Abstract
Metastasis is a multistep process that implies genetic modifications and is strongly influenced by the interactions between host and tumor cells, and by tumor microenvironment. Before tumor cells colonize distant organs, they can prepare foreign soil by remotely coordinating a “premetastatic niche” from the primary tumor. The premetastatic niche provides an array of cells, cytokines, growth factors, and adhesion molecules to support metastatic cells on their arrival and to guide metastases to specific organs. Factors secreted by tumor cells, such as VEGF, LOX, IL-6, IL-10, and exosomes, participate in the premetastatic niche formation. Also extracellular matrix (ECM) molecules, namely periostin, tenascin and osteopontin can supply the necessary resources for successful metastatic colonization. One of the key underlying hypotheses of the cancer stem cell (CSC) model proposes that CSCs are the basis of metastases. CSCs in situ may transform to metastatic stem cells (MetSCs) by epithelial-mesenchymal transition (EMT) and subsequently disseminate and form metastatic colonies. Alternatively, MetSCs may derive from disseminated tumor cells that reacquire the competence to initiate tumor growth after a period of indolence. CSCs exhibit properties that are beneficial to metastasize and adapt in the foreign microenvironment, such as mesenchymal characteristics, increased capacity for DNA repair, resistance to apoptosis and to antitumor therapy. Circulating tumor cells (CTCs) are linked to tumor progression in a variety of solid tumors. CTCs are therefore assumed as precursors of distant metastasis. Potentially, a fraction of CTCs have CSC activity; stem-like CTCs may be a critical subset of CTCs with the capacity to form distant metastases. Many therapeutic strategies against CSCs strategies have been investigated. Among them, therapies directed at CSC niche and pre-metastatic niche are of particular interest. These therapies are aimed at targeting vasculature, extrinsic signals and tumor associated macrophages.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Acharyya S, Oskarsson T, Vanharanta S, Malladi S, Kim J, Morris PG et al (2012) A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell 150(1):165–178
Aguirre-Ghiso JA (2007) Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer 7:834–846
Aktas B, Tewes M, Fehm T, Hauch S, Kimmig R, Kasimir-Bauer S (2009) Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res 11(4):R46
Allavena P, Signorelli M, Chieppa M, Erba E, Bianchi G, Marchesi F et al (2005) Anti-inflammatory properties of the novel anti-tumor agent yondelis (trabectedin): inhibition of macrophage differentiation and cytokine production. Cancer Res 65(7):2964–2971
Allavena P, Sica A, Solinas G, Porta C, Mantovani A (2008) The inflammatory micro-environment in tumor progression: the role of tumor-associated macrophages. Crit Rev Oncol Hematol 66(1):1–9
Al-Mehdi AB, Tozawa K, Fisher AB, Shientag L, Lee A, Muschel RJ (2000) Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nat Med 6(1):100–102
Andres JL, Rönnstrand L, Cheifetz S, Massagué J (1991) Purification of the transforming growth factor-beta (TGF-beta) binding proteoglycan betaglycan. J Biol Chem 266(34):23282–23287
Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279(5349):377–380
Armstrong AJ, Marengo MS, Oltean S, Kemeny G, Bitting RL, Turnbull JD et al (2011) Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol Cancer Res 9(8):997–1007
Asselin-Labat ML, Vaillant F, Sheridan JM, Pal B, Wu D, Simpson ER et al (2010) Control of mammary stem cell function by steroid hormone signalling. Nature 465(7299):798–802
Azab AK, Runnels JM, Pitsillides C, Moreau AS, Azab F, Leleu X et al (2009) CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy. Blood 113(18):4341–4351
Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A, Vogel V et al (2013) Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol 31(6):539–544
Balic M, Lin H, Young L, Hawes D, Giuliano A, McNamara G et al (2006) Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res 2(19):5615–5621
Bandyopadhyay S, Zhan R, Chaudhuri A, Watabe M, Pai SK, Hirota S et al (2006) Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression. Nat Med 12(8):933–938
Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB et al (2006a) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444(7120):756–760
Bao S, Wu Q, Sathornsumetee S, Hao Y, Li Z, Hjelmeland AB et al (2006b) Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res 66(16):7843–7848
Barkan D, Green JE, Chambers AF (2010) Extracellular matrix: a gatekeeper in the transition from dormancy to metastatic growth. Eur J Cancer 46(7):1181–1188
Barone A, Sengupta R, Warrington NM, Smith E, Wen PY, Brekken RA et al (2014) Combined VEGF and CXCR4 antagonism targets the GBM stem cell population and synergistically improves survival in an intracranial mouse model of glioblastoma. Oncotarget
Barrière G, Riouallon A, Renaudie J, Tartary M, Rigaud M (2012) Mesenchymal and stemness circulating tumor cells in early breast cancer diagnosis. BMC Cancer 12:114
Bautch VL (2011) Stem cells and the vasculature. Nat Med 17(11):1437–1443
Behrens J (1994–1995) Cell contacts, differentiation, and invasiveness of epithelial cells. Invasion Metastasis 14(1–6):61–70
Beier D, Wischhusen J, Dietmaier W, Hau P, Proescholdt M, Brawanski A et al (2008) CD133 expression and cancer stem cells predict prognosis in high-grade oligodendroglial tumors. Brain Pathol 18(3):370–377
Bergers G, Benjamin LE (2003) Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3(6):401–410
Biswas SK, Sica A, Lewis CE (2008) Plasticity of macrophage function during tumor progression: regulation by distinct molecular mechanisms. J Immunol 180(4):2011–2017
Blaheta RA, Michaelis M, Driever PH, Cinatl J Jr (2005) Evolving anticancer drug valproic acid: insights into the mechanism and clinical studies. Med Res Rev 25(4):383–397
Borovski T, Verhoeff JJ, Cate R, Cameron K, de Vries NA, van Tellingen O et al (2009) Tumor microvasculature supports proliferation and expansion of glioma-propagating cells. Int J Cancer 125(5):1222–1230
Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF et al (1991) Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 251(4995):802–804
Brabletz T (2012) To differentiate or not–routes towards metastasis. Nat Rev Cancer 12(6):425–436
Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T (2005) Opinion: migrating cancer stem cells – an integrated concept of malignant tumour progression. Nat Rev Cancer 5(9):744–749
Burnett AK, Hills RK, Green C, Jenkinson S, Koo K, Patel Y et al (2010) The impact on outcome of the addition of all-trans retinoic acid to intensive chemotherapy in younger patients with nonacute promyelocytic acute myeloid leukemia: overall results and results in genotypic subgroups defined by mutations in NPM1, FLT3, and CEBPA. Blood 115(5):948–956
Butler JM, Kobayashi H, Rafii S (2010) Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors. Nat Rev Cancer 10(2):138–146
Cairns J (2002) Somatic stem cells and the kinetics of mutagenesis and carcinogenesis. Proc Natl Acad Sci U S A 99(16):10567–10570
Calabrese C, Poppleton H, Kocak M, Hogg TL, Fuller C, Hamner B et al (2007) A perivascular niche for brain tumor stem cells. Cancer Cell 11(1):69–82
Calon A, Espinet E, Palomo-Ponce S, Tauriello DV, Iglesias M, Céspedes MV et al (2012) Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation. Cancer Cell 22(5):571–584
Cameron MD, Schmidt EE, Kerkvliet N, Nadkarni KV, Morris VL, Groom AC et al (2000) Temporal progression of metastasis in lung: cell survival, dormancy, and location dependence of metastatic inefficiency. Cancer Res 60(9):2541–2546
Carbonell WS, Ansorge O, Sibson N, Muschel R (2009) The vascular basement membrane as “soil” in brain metastasis. PLoS One 4(6), e5857
Cavallaro U, Christofori G (2004) Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer 4(2):118–132
Chaffer CL, Dopheide B, McCulloch DR, Lee AB, Moseley JM, Thompson EW et al (2005) Upregulated MT1-MMP/TIMP-2 axis in the TSU-Pr1-B1/B2 model of metastatic progression in transitional cell carcinoma of the bladder. Clin Exp Metastasis 22(2):115–125
Chaffer CL, Brennan JP, Slavin JL, Blick T, Thompson EW, Williams ED (2006) Mesenchymal-to-epithelial transition facilitates bladder cancer metastasis: role of fibroblast growth factor receptor-2. Cancer Res 66(23):11271–11278
Chaffer CL, Thompson EW, Williams ED (2007) Mesenchymal to epithelial transition in development and disease. Cells Tissues Organs 185(1-3):7–19
Chakrabarty S, Fan D, Varani J (1990) Modulation of differentiation and proliferation in human colon carcinoma cells by transforming growth factor beta 1 and beta 2. Int J Cancer 46(3):493–499
Chakraborty G, Jain S, Kundu GC (2008) Osteopontin promotes vascular endothelial growth factor-dependent breast tumor growth and angiogenesis via autocrine and paracrine mechanisms. Cancer Res 68(1):152–161
Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2(8):563–572
Chao YL, Shepard CR, Wells A (2010) Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition. Mol Cancer 9:179
Charafe-Jauffret E, Ginestier C, Iovino F, Tarpin C, Diebel M, Esterni B et al (2010) Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer. Clin Cancer Res 16(1):45–55
Charles N, Holland EC (2010) The perivascular niche microenvironment in brain tumor progression. Cell Cycle 9(15):3012–3021 (B)
Charles N, Ozawa T, Squatrito M, Bleau AM, Brennan CW, Hambardzumyan D et al (2010) Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells. Cell Stem Cell 6(2):141–152
Chauhan P, Sodhi A, Shrivastava A (2009) Cisplatin primes murine peritoneal macrophages for enhanced expression of nitric oxide, proinflammatory cytokines, TLRs, transcription factors and activation of MAP kinases upon co-incubation with L929 cells. Immunobiology 214:197–209
Chen Q, Zhang XH, Massagué J (2011) Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs. Cancer Cell 20(4):538–549
Cheng F, Wang HW, Cuenca A, Huang M, Ghansah T, Brayer J et al (2003) A critical role for Stat3 signaling in immune tolerance. Immunity 19(3):425–436
Chiang AC, Massagué J (2008) Molecular basis of metastasis. N Engl J Med 359(26):2814–2823
Clevers H (2006) Wnt/beta-catenin signaling in development and disease. Cell 127(3):469–480
Clevers H (2013) The intestinal crypt, a prototype stem cell compartment. Cell 154(2):274–284
Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY et al (2008) Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 26(19):3213–3221
Cojoc M, Peitzsch C, Trautmann F, Polishchuk L, Telegeev GD, Dubrovska A (2013) Emerging targets in cancer management: role of the CXCL12/CXCR4 axis. Onco Targets Ther 6:1347–1361
Comen E, Norton L (2012) Self-seeding in cancer. Recent Results Cancer Res 195:13–23
Condeelis J, Segall JE (2003) Intravital imaging of cell movement in tumours. Nat Rev Cancer 3(12):921–930
Conley SJ, Gheordunescu E, Kakarala P, Newman B, Korkaya H, Heath AN et al (2012) Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia. Proc Natl Acad Sci U S A 109(8):2784–2789
Conticello C, Pedini F, Zeuner A, Patti M, Zerilli M, Stassi G et al (2004) IL-4 protects tumor cells from anti-CD95 and chemotherapeutic agents via up-regulation of antiapoptotic proteins. J Immunol 172(9):5467–5477
Coscia M, Quaglino E, Iezzi M, Curcio C, Pantaleoni F, Riganti C et al (2010) Zoledronic acid repolarizes tumour-associated macrophages and inhibits mammary carcinogenesis by targeting the mevalonate pathway. J Cell Mol Med 14(12):2803–2815
Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867
Coward J, Kulbe H, Chakravarty P, Leader D, Vassileva V, Leinster DA et al (2011) Interleukin-6 as a therapeutic target in human ovarian cancer. Clin Cancer Res 17(18):6083–6096
Cramer T, Yamanishi Y, Clausen BE, Förster I, Pawlinski R, Mackman N et al (2003) HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell 112(5):645–657
Criscuoli ML, Nguyen M, Eliceiri BP (2005) Tumor metastasis but not tumor growth is dependent on Src-mediated vascular permeability. Blood 105:1508
Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351(8):781–791
Cristofanilli M, Hayes DF, Budd GT, Ellis MJ, Stopeck A, Reuben JM et al (2005) Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23(7):1420–1430
Croker AK, Allan AL (2012) Inhibition of aldehyde dehydrogenase (ALDH) activity reduces chemotherapy and radiation resistance of stem-like ALDHhiCD44+ human breast cancer cells. Breast Cancer Res Treat 133(1):75–87
Crowley NJ, Seigler HF (1992) Relationship between disease-free interval and survival in patients with recurrent melanoma. Arch Surg 127(11):1303–1308
D’Alterio C, Barbieri A, Portella L, Palma G, Polimeno M, Riccio A et al (2012) Inhibition of stromal CXCR4 impairs development of lung metastases. Cancer Immunol Immunother 61(10):1713–1720
D’Andrea FP (2012) Intrinsic radiation resistance of mesenchymal cancer stem cells and implications for treatment response in a murine sarcoma model. Dan Med J 59(2):B4388
Dameron KM, Volpert OV, Tainsky MA, Bouck N (1994) Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science 265(5178):1582–1584
Damonte P, Gregg JP, Borowsky AD, Keister BA, Cardiff RD (2007) EMT tumorigenesis in the mouse mammary gland. Lab Invest 87(12):1218–1226
Dangi-Garimella S, Yun J, Eves EM, Newman M, Erkeland SJ, Hammond SM et al (2009) Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7. EMBO J 28(4):347–358
Danila DC, Heller G, Gignac GA, Gonzalez-Espinoza R, Anand A, Tanaka E et al (2007) Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer. Clin Cancer Res 13(23):7053–7058
Dannenberg AJ, Subbaramaiah K (2003) Targeting cyclooxygenase-2 in human neoplasia: rationale and promise. Cancer Cell 4(6):431–436
De Nigris F, Schiano C, Infante T, Napoli C (2012) CXCR4 inhibitors: tumor vasculature and therapeutic challenges. Recent Pat Anticancer Drug Discov 7(3):251–264
de Sousa EM, Vermeulen L, Richel D, Medema JP (2011) Targeting Wnt signaling in colon cancer stem cells. Clin Cancer Res 17(4):647–653
Dean M (2009) ABC transporters, drug resistance, and cancer stem cells. J Mammary Gland Biol Neoplasia 14(1):3–9
Debeb BG, Xu W, Woodward WA (2009) Radiation resistance of breast cancer stem cells: understanding the clinical framework. J Mammary Gland Biol Neoplasia 14(1):11–17
Demicheli R, Abbattista A, Miceli R, Valagussa P, Bonadonna G (1996) Time distribution of the recurrence risk for breast cancer patients undergoing mastectomy: further support about the concept of tumor dormancy. Breast Cancer Res Treat 41(2):177–185
Deng J, Liu Y, Lee H, Herrmann A, Zhang W, Zhang C et al (2012) S1PR1-STAT3 signaling is crucial for myeloid cell colonization at future metastatic sites. Cancer Cell 21(5):642–654
Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ, Kulp AN et al (2009) Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 458(7239):780–783
Dieter SM, Ball CR, Hoffmann CM, Nowrouzi A, Herbst F, Zavidij O et al (2011) Distinct types of tumor-initiating cells form human colon cancer tumors and metastases. Cell Stem Cell 9(4):357–365
Dineen SP, Lynn KD, Holloway SE, Miller AF, Sullivan JP, Shames DS et al (2008) Vascular endothelial growth factor receptor 2 mediates macrophage infiltration into orthotopic pancreatic tumors in mice. Cancer Res 68(11):4340–4346
Ding XW, Wu JH, Jiang CP (2010) ABCG2: a potential marker of stem cells and novel target in stem cell and cancer therapy. Life Sci 86(17-18):631–637
Doberstein K, Wieland A, Lee SB, Blaheta RA, Wedel S, Moch H et al (2011) L1-CAM expression in ccRCC correlates with shorter patients survival times and confers chemoresistance in renal cell carcinoma cells. Carcinogenesis 32(3):262–270
Doedens AL, Stockmann C, Rubinstein MP, Liao D, Zhang N, DeNardo DG et al (2010) Macrophage expression of hypoxia-inducible factor-1 alpha suppresses T-cell function and promotes tumor progression. Cancer Res 70(19):7465–7475
Domanska UM, Timmer-Bosscha H, Nagengast WB, Oude Munnink TH, Kruizinga RC, Ananias HJ et al (2012) CXCR4 inhibition with AMD3100 sensitizes prostate cancer to docetaxel chemotherapy. Neoplasia 14(8):709–718
Donnenberg VS, Meyer EM, Donnenberg AD (2009) Measurement of multiple drug resistance transporter activity in putative cancer stem/progenitor cells. Methods Mol Biol 568:261–279
Draffin JE, McFarlane S, Hill A, Johnston PG, Waugh DJ (2004) CD44 potentiates the adherence of metastatic prostate and breast cancer cells to bone marrow endothelial cells. Cancer Res 64:5702–5711
Du R, Lu KV, Petritsch C, Liu P, Ganss R, Passegué E et al (2008) HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell 3(3):206–220
Dubrovska A, Elliott J, Salamone RJ, Kim S, Aimone LJ, Walker JR et al (2010) Combination therapy targeting both tumor-initiating and differentiated cell populations in prostate carcinoma. Clin Cancer Res 16(23):5692–56702
Dubrovska A, Hartung A, Bouchez LC, Walker JR, Reddy VA, Cho CY et al (2012) CXCR4 activation maintains a stem cell population in tamoxifen-resistant breast cancer cells through AhR signalling. Br J Cancer 107(1):43–52
Duncan AW, Rattis FM, DiMascio LN, Congdon KL, Pazianos G, Zhao C et al (2005) Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol 6(3):314–322
Dunn GP, Koebel CM, Schreiber RD (2006) Interferons, immunity and cancer immunoediting. Nat Rev Immunol 6(11):836–848
Dvorak HF, Senger DR, Dvorak AM (1983) Fibrin as a component of the tumor stroma: origins and biological significance. Cancer Metastasis Rev 2(1):41–73
Ebos JM, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS (2009) Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 15:232–239
Edwards JP, Emens LA (2010) The multikinase inhibitor sorafenib reverses the suppression of IL-12 and enhancement of IL-10 by PGE2 in murine macrophages. Int Immunopharmacol 10:1220–1228
Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2(3):161–174
el-Sabban ME, Pauli BU (1994–1995) Adhesion-mediated gap junctional communication between lung-metastatic cancer cells and endothelium. Invasion Metastasis 14(1–6):164–176
Erler JT, Cawthorne CJ, Williams KJ, Koritzinsky M, Wouters BG, Wilson C et al (2004) Hypoxia-mediated down-regulation of Bid and Bax in tumors occurs via hypoxia-inducible factor 1-dependent and -independent mechanisms and contributes to drug resistance. Mol Cell Biol 24(7):2875–2889
Erler JT, Bennewith KL, Cox TR, Lang G, Bird D, Koong A et al (2009) Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell 15(1):35–44
Fang HY, Hughes R, Murdoch C, Coffelt SB, Biswas SK, Harris AL et al (2009) Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia. Blood 114(4):844–859
Fehm T, Sagalowsky A, Clifford E, Beitsch P, Saboorian H, Euhus D et al (2002) Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant. Clin Cancer Res 8(7):2073–2084
Fehm T, Hoffmann O, Aktas B, Becker S, Solomayer EF, Wallwiener D et al (2009) Detection and characterization of circulating tumor cells in blood of primary breast cancer patients by RT-PCR and comparison to status of bone marrow disseminated cells. Breast Cancer Res 11(4):R59
Fehm T, Müller V, Aktas B, Janni W, Schneeweiss A, Stickeler E et al (2010) HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res Treat 124(2):403–412
Felding-Habermann B, O’Toole TE, Smith JW, Fransvea E, Ruggeri ZM, Ginsberg MH et al (2001) Integrin activation controls metastasis in human breast cancer. Proc Natl Acad Sci U S A 98(4):1853–1858
Feldmann G, Fendrich V, McGovern K, Bedja D, Bisht S, Alvarez H et al (2008) An orally bioavailable small-molecule inhibitor of Hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer. Mol Cancer Ther 7:2725–2735
Ferrari P, Nicolini A (2012) Breast cancer stem cells: new therapeutic approaches. Breast Cancer Manag 1(4):277–294
Ferrari P, Nicolini A, Carpi A (2013) Targeted therapies of metastatic breast cancer: relationships with cancer stem cells. Biomed Pharmacother 67(6):543–555
Fidler IJ (2001) Seed and soil revisited: contribution of the organ microenvironment to cancer metastasis. Surg Oncol Clin N Am 10(2):257–269
Fidler IJ (2003) The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 3:453–458
Floor S, van Staveren WC, Larsimont D, Dumont JE, Maenhaut C (2011) Cancer cells in epithelial-to-mesenchymal transition and tumor-propagating-cancer stem cells: distinct, overlapping or same populations. Oncogene 30(46):4609–4621
Fodde R, Brabletz T (2007) Wnt/beta-catenin signaling in cancer stemness and malignant behavior. Curr Opin Cell Biol 19(2):150–158
Folkins C, Man S, Xu P, Shaked Y, Hicklin DJ, Kerbel RS (2007) Anticancer therapies combining antiangiogenic and tumor cell cytotoxic effects reduce the tumor stem-like cell fraction in glioma xenograft tumors. Cancer Res 67:3560–3564
Friedl P, Wolf K (2003) Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3(5):362–374
Friedrichs K, Franke F, Lisboa BW, Kügler G, Gille I, Terpe HJ et al (1995) CD44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer. Cancer Res 55(22):5424–5433
Frisch SM, Screaton RA (2001) Anoikis mechanisms. Curr Opin Cell Biol 13(5):555–562
Galsky MD, Vogelzang NJ, Conkling P, Raddad E, Polzer J, Roberson S et al (2014) A phase I trial of LY2510924, a CXCR4 peptide antagonist, in patients with advanced cancer. Clin Cancer Res 20(13):3581–3588
Gao D, Nolan DJ, Mellick AS, Bambino K, McDonnell K, Mittal V (2008) Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science 319(5860):195–198
Gao H, Chakraborty G, Lee-Lim AP, Mo Q, Decker M, Vonica A et al (2012) The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites. Cell 150(4):764–779
Garcia A, Kandel JJ (2012) Notch: a key regulator of tumor angiogenesis and metastasis. Histol Histopathol 27(2):151–156
Gasic GJ (1984) Role of plasma, platelets, and endothelial cells in tumor metastasis. Cancer Metastasis Rev 3(2):99–114
Gassenmaier M, Chen D, Buchner A, Henkel L, Schiemann M, Mack B et al (2013) CXC chemokine receptor 4 is essential for maintenance of renal cell carcinoma-initiating cells and predicts metastasis. Stem Cells 31(8):1467–1476
Gatenby RA, Gillies RJ (2004) Why do cancers have high aerobic glycolysis? Nat Rev Cancer 4(11):891–899
Germano G, Frapolli R, Simone M, Tavecchio M, Erba E, Pesce S et al (2010) Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells. Cancer Res 70(6):2235–2244
Ghajar CM, Peinado H, Mori H, Matei IR, Evason KJ, Brazier H et al (2013) The perivascular niche regulates breast tumour dormancy. Nat Cell Biol 15(7):807–817
Giaccia AJ, Erler JT (2008) The cellular microenvironment and metastases. In: Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG (eds) Clinical oncology, 4th edn. Churchill Livingstone-Elsevier, Philadelphia, pp 1177–1228 (Chapter 3)
Giancotti FG (2013) Mechanisms governing metastatic dormancy and reactivation. Cell 155(4):750–764
Gil M, Komorowski MP, Seshadri M, Rokita H, McGray AJ, Opyrchal M et al (2014) CXCL12/CXCR4 blockade by oncolytic virotherapy inhibits ovarian cancer growth by decreasing immunosuppression and targeting cancer-initiating cells. J Immunol
Gil-Bernabé AM, Ferjancic S, Tlalka M, Zhao L, Allen PD, Im JH et al (2012) Recruitment of monocytes/macrophages by tissue factor-mediated coagulation is essential for metastatic cell survival and premetastatic niche establishment in mice. Blood 119(13):3164–3175
Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M et al (2010) CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest 120(2):485–497
Giordano A, Gao H, Anfossi S, Cohen E, Mego M, Lee BN et al (2012) Epithelial-mesenchymal transition and stem cell markers in patients with HER2-positive metastatic breast cancer. Mol Cancer Ther 11(11):2526–2534
Goodison S, Kawai K, Hihara J, Jiang P, Yang M, Urquidi V et al (2003) Prolonged dormancy and site-specific growth potential of cancer cells spontaneously disseminated from nonmetastatic breast tumors as revealed by labeling with green fluorescent protein. Clin Cancer Res 9(10, Pt 1):3808–3814
Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe SW et al (1996) Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 379(6560):88–91
Grange C, Tapparo M, Collino F, Vitillo L, Damasco C, Deregibus MC et al (2011) Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche. Cancer Res 71(15):5346–5356
Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G et al (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 10(5):593–601
Gross ME, Zorbas MA, Danels YJ, Garcia R, Gallick GE, Olive M et al (1991) Cellular growth response to epidermal growth factor in colon carcinoma cells with an amplified epidermal growth factor receptor derived from a familial adenomatous polyposis patient. Cancer Res 51(5):1452–1459
Guo W, Giancotti FG (2004) Integrin signalling during tumor progression. Nat Rev Mol Cell Biol 5:816
Guo C, Sah JF, Beard L, Willson JK, Markowitz SD, Guda K (2008) The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers. Genes Chromosomes Cancer 47(11):939–946
Gupta GP, Massagué J (2006) Cancer metastasis: building a framework. Cell 127(4):679–695
Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA et al (2009) Identification of selective inhibitors of cancer stem cells by high-throughput screening 1. Cell 138:645–659
Hambardzumyan D, Becher OJ, Holland EC (2008) Cancer stem cells and survival pathways. Cell Cycle 7(10):1371–1378
Hanada T, Nakagawa M, Emoto A, Nomura T, Nasu N, Nomura Y (2000) Prognostic value of tumor-associated macrophage count in human bladder cancer. Int J Urol 7:263–269
Havens AM, Pedersen EA, Shiozawa Y, Ying C, Jung Y, Sun Y et al (2008) An in vivo mouse model for human prostate cancer metastasis. Neoplasia 10(4):371–380
Heddleston JM, Li Z, McLendon RE, Hjelmeland AB, Rich JN (2009) The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype. Cell Cycle 8(20):3274–3284
Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M et al (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1(3):313–323
Hess KR, Varadhachary GR, Taylor SH, Wei W, Raber MN, Lenzi R et al (2006) Metastatic patterns in adenocarcinoma. Cancer 106(7):1624–1633
Hill RP, Marie-Egyptienne DT, Hedley DW (2009) Cancer stem cells, hypoxia and metastasis. Semin Radiat Oncol 19:106–111
Hiraoka K, Zenmyo M, Watari K, Iguchi H, Fotovati A, Kimura YN et al (2008) Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages. Cancer Sci 99(8):1595–1602
Hiratsuka S, Nakamura K, Iwai S, Murakami M, Itoh T, Kijima H et al (2002) MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer Cell 2(4):289–300
Hiratsuka S, Watanabe A, Aburatani H, Maru Y (2006) Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol 8(12):1369–1375
Hiratsuka S, Watanabe A, Sakurai Y, Akashi-Takamura S, Ishibashi S, Miyake K et al (2008) The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol 10(11):1349–1355
Hoey T, Yen WC, Axelrod F, Basi J, Donigian L, Dylla S et al (2009) DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency. Cell Stem Cell 5:168–177
Hoffman PC, Mauer AM, Vokes EE (2000) Lung cancer. Lancet 355:479–485
Holmgren L, O’Reilly MS, Folkman J (1995) Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1:149–153
Hood JL, San RS, Wickline SA (2011) Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res 71:3792–3801
Hope KJ, Jin L, Dick JE (2004) Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 5(7):738–743
Horst D, Kriegl L, Engel J, Kirchner T, Jung A (2009) Prognostic significance of the cancer stem cell markers CD133, CD44, and CD166 in colorectal cancer. Cancer Invest 27(8):844–850
Hovinga KE, Shimizu F, Wang R, Panagiotakos G, Van Der Heijden M, Moayedpardazi H et al (2010) Inhibition of notch signaling in glioblastoma targets cancer stem cells via an endothelial cell intermediate. Stem Cells 28(6):1019–1029
Hsu YC, Fuchs E (2012) A family business: stem cell progeny join the niche to regulate homeostasis. Nat Rev Mol Cell Biol 13(2):103–114
Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED et al (2007) Epithelial–mesenchymal and mesenchymal–epithelial transitions in carcinoma progression. J Cell Physiol 213(2):374–383
Iliopoulos D, Hirsch HA, Struhl K (2009) An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 139(4):693–706
Imai T, Horiuchi A, Shiozawa T, Osada R, Kikuchi N, Ohira S et al (2004) Elevated expression of E-cadherin and alpha-, beta-, and gamma-catenins in metastatic lesions compared with primary epithelial ovarian carcinomas. Hum Pathol 35(12):1469–1476
Imtiyaz HZ, Williams EP, Hickey MM, Patel SA, Durham AC, Yuan LJ et al (2010) Hypoxia-inducible factor 2alpha regulates macrophage function in mouse models of acute and tumor inflammation. J Clin Invest 120(8):2699–2714
Ishikawa T, Nakashiro K, Klosek SK, Goda H, Hara S, Uchida D et al (2009) Hypoxia enhances CXCR4 expression by activating HIF-1 in oral squamous cell carcinoma. Oncol Rep 21(3):707–712
Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE (2006) Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med 12:1167–1174
Jin L, Lee EM, Ramshaw HS, Busfield SJ, Peoppl AG, Wilkinson L et al (2009) Monoclonal antibody-mediated targeting of CD123, IL-3 receptor alpha chain, eliminates human acute myeloid leukemic stem cells. Cell Stem Cell 5:31–42
Jin G, Kawsar HI, Hirsch SA, Zeng C, Jia X, Feng Z et al (2010) An antimicrobial peptide regulates tumor-associated macrophage trafficking via the chemokine receptor CCR2, a model for tumorigenesis. PLoS One 5(6), e10993
Jordan NV, Johnson GL, Abell AN (2011) Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancer. Cell Cycle 10(17):2865–2873
Joseph J, Shiozawa Y, Jung Y, Kim JK, Pedersen E, Mishra A et al (2012) Disseminated prostate cancer cells can instruct hematopoietic stem and progenitor cells to regulate bone phenotype. Mol Cancer Res 10:282–292
Joshi PA, Jackson HW, Beristain AG, Di Grappa MA, Mote PA, Clarke CL et al (2010) Progesterone induces adult mammary stem cell expansion. Nature 465(7299):803–807
Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev Cancer 9(4):239–252
Jung MJ, Rho JK, Kim YM, Jung JE, Jin YB, Ko YG et al (2013) Upregulation of CXCR4 is functionally crucial for maintenance of stemness in drug-resistant non-small cell lung cancer cells. Oncogene 32(2):209–221
Kajiyama H, Shibata K, Terauchi M, Ino K, Nawa A, Kikkawa F (2008) Involvement of SDF-1alpha/CXCR4 axis in the enhanced peritoneal metastasis of epithelial ovarian carcinoma. Int J Cancer 122(1):91–99
Kalikin LM, Schneider A, Thakur MA, Fridman Y, Griffin LB, Dunn RL et al (2003) In vivo visualization of metastatic prostate cancer and quantitation of disease progression in immunocompromised mice. Cancer Biol Ther 2(6):656–660
Kallergi G, Papadaki MA, Politaki E, Mavroudis D, Georgoulias V, Agelaki S (2011) Epithelial to mesenchymal transition markers expressed in circulating tumour cells of early and metastatic breast cancer patients. Breast Cancer Res 13(3):R59
Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordón-Cardo C et al (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3(6):537–549
Kantara C, O’Connell MR, Luthra G, Gajjar A, Sarkar S, Ullrich RL et al (2015) Methods for detecting circulating cancer stem cells (CCSCs) as a novel approach for diagnosis of colon cancer relapse/metastasis. Lab Invest 95:100–112
Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C et al (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438(7069):820–827
Kaplan RN, Rafii S, Lyden D (2006) Preparing the “soil”: the premetastatic niche. Cancer Res 66(23):11089–11093
Kaplan RN, Psaila B, Lyden D (2007) Niche-to-niche migration of bone-marrow-derived cells. Trends Mol Med 13(2):72–81
Karin M (2006) Nuclear factor-kappaB in cancer development and progression. Nature 441(7092):431–436
Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW et al (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449(7162):557–563
Karpatkin S, Pearlstein E (1981) Role of platelets in tumor cell metastases. Ann Intern Med 95(5):636–641
Karpatkin S, Pearlstein E, Ambrogio C, Coller BS (1988) Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. J Clin Invest 81(4):1012–1019
Kasimir-Bauer S, Hoffmann O, Wallwiener D, Kimmig R, Fehm T (2012) Expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells. Breast Cancer Res 14(1):R15
Khatib AM, Auguste P, Fallavollita L, Wang N, Samani A, Kontogiannea M et al (2005) Characterization of the host proinflammatory response to tumor cells during the initial stages of liver metastasis. Am J Pathol 167(3):749–759
Kienast Y, von Baumgarten L, Fuhrmann M, Klinkert WE, Goldbrunner R, Herms J et al (2010) Real-time imaging reveals the single steps of brain metastasis formation. Nat Med 16(1):116–122
Kii I, Nishiyama T, Li M, Matsumoto K, Saito M, Amizuka N et al (2010) Incorporation of tenascin-C into the extracellular matrix by periostin underlies an extracellular meshwork architecture. J Biol Chem 285(3):2028–2039
Kim YJ, Borsig L, Varki NM, Varki A (1998) P-selectin deficiency attenuates tumor growth and metastasis. Proc Natl Acad Sci U S A 95(16):9325–9330
Kim MY, Oskarsson T, Acharyya S, Nguyen DX, Zhang XH, Norton L et al (2009) Tumor self-seeding by circulating cancer cells. Cell 139(7):1315–1326
Kim M, Koh YJ, Kim KE, Koh BI, Nam DH, Alitalo K et al (2010) CXCR4 signaling regulates metastasis of chemoresistant melanoma cells by a lymphatic metastatic niche. Cancer Res 70(24):10411–10421
Kim E, Kim M, Woo DH, Shin Y, Shin J, Chang N et al (2013) Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma stem-like cells. Cancer Cell 23(6):839–852
Kioi M, Vogel H, Schultz G, Hoffman RM, Harsh GR, Brown JM (2010) Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J Clin Invest 120(3):694–705
Klein CA (2009) Parallel progression of primary tumours and metastases. Nat Rev Cancer 9(4):302–312
Klein CA (2011) Framework models of tumor dormancy from patient-derived observations. Curr Opin Genet Dev 21(1):42–49
Knowles HJ, Harris AL (2001) Hypoxia and oxidative stress in breast cancer. Hypoxia and tumourigenesis. Breast Cancer Res 3(5):318–322
Knowles H, Leek R, Harris AL (2004) Macrophage infiltration and angiogenesis in human malignancy. Novartis Found Symp 256:189–200
Kobayashi CI, Suda T (2012) Regulation of reactive oxygen species in stem cells and cancer stem cells. J Cell Physiol 227(2):421–430
Kobayashi A, Okuda H, Xing F, Pandey PR, Watabe M, Hirota S et al (2011) Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone. J Exp Med 208(13):2641–2655
Korkaya H, Liu S, Wicha MS (2011) Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest 121(10):3804–3809
Kowalski PJ, Rubin MA, Kleer CG (2003) E-cadherin expression in primary carcinomas of the breast and its distant metastases. Breast Cancer Res 5(6):R217–R222
Krantz SB, Shields MA, Dangi-Garimella S, Munshi HG, Bentrem DJ (2012) Contribution of epithelial-to-mesenchymal transition and cancer stem cells to pancreatic cancer progression. J Surg Res 173(1):105–112
Kubota Y, Takubo K, Shimizu T, Ohno H, Kishi K, Shibuya M et al (2009) MCSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. J Exp Med 206:1089–1102
Kurahara H, Shinchi H, Mataki Y, Maemura K, Noma H, Kubo F et al (2011) Significance of M2-polarized tumor-associated macrophage in pancreatic cancer. J Surg Res 167(2):e211–e219
Kurahara H, Takao S, Kuwahata T, Nagai T, Ding Q, Maeda K et al (2012) Clinical significance of folate receptor β-expressing tumor-associated macrophages in pancreatic cancer. Ann Surg Oncol 19(7):2264–2271
Labelle M, Begum S, Hynes RO (2011) Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell 20(5):576–590
Larson CJ, Moreno JG, Pienta KJ, Gross S, Repollet M, O’hara SM et al (2004) Apoptosis of circulating tumor cells in prostate cancer patients. Cytometry A 62(1):46–53
Le QT, Denko NC, Giaccia AJ (2004) Hypoxic gene expression and metastasis. Cancer Metastasis Rev 23(3-4):293–310
Lee JM, Dedhar S, Kalluri R, Thompson EW (2006) The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol 172(7):973–981
Lee TK, Cheung VC, Ng IO (2013) Liver tumor-initiating cells as a therapeutic target for hepatocellular carcinoma. Cancer Lett 338:101–109
Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246(4935):1306–1309
Lewis CE, Pollard JW (2006) Distinct role of macrophages in different tumor microenvironments. Cancer Res 66:605–612
Li Z, Rich JN (2010) Hypoxia and hypoxia inducible factors in cancer stem cell maintenance. Curr Top Microbiol Immunol 345:21–30
Li HJ, Reinhardt F, Herschman HR, Weinberg RA (2012) Cancer-stimulated mesenchymal stem cells create a carcinoma stem cell niche via prostaglandin E2 signaling. Cancer Discov 2(9):840–855
Liang W, Kujawski M, Wu J, Lu J, Herrmann A, Loera S et al (2010) Antitumor activity of targeting SRC kinases in endothelial and myeloid cell compartments of the tumor microenvironment. Clin Cancer Res 16(3):924–935
Lianidou ES, Mavroudis D, Georgoulias V (2013) Clinical challenges in the molecular characterization of circulating tumour cells in breast cancer. Br J Cancer 108(12):2426–2432
Liao X, Sharma N, Kapadia F, Zhou G, Lu Y, Hong H et al (2011) Krüppel-like factor 4 regulates macrophage polarization. J Clin Invest 121(7):2736–2749
Liu H, Patel MR, Prescher JA, Patsialou A, Qian D, Lin J et al (2010) Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. Proc Natl Acad Sci U S A 107(42):18115–18120
Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H et al (2011a) The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med 17:211–215
Liu S, Ginestier C, Ou SJ, Clouthier SG, Patel SH, Monville F et al (2011b) Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Res 71(2):614–624
Lonardo E, Hermann PC, Mueller MT, Huber S, Balic A, Miranda-Lorenzo I et al (2011) Nodal/Activin signaling drives self-renewal and tumorigenicity of pancreatic cancer stem cells and provides a target for combined drug therapy. Cell Stem Cell 9(5):433–446
Lou H, Dean M (2007) Targeted therapy for cancer stem cells: the patched pathway and ABC transporters. Oncogene 26(9):1357–1360
Louissaint A Jr, Rao S, Leventhal C, Goldman SA (2002) Coordinated interaction of neurogenesis and angiogenesis in the adult songbird brain. Neuron 34(6):945–960
Lowes LE, Hedley BD, Keeney M, Allan AL (2012) User-defined protein marker assay development for characterization of circulating tumor cells using the Cell Search® system. Cytometry A 81(11):983–995
Lu X, Mu E, Wei Y, Riethdorf S, Yang Q, Yuan M et al (2011) VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging α4β1-positive osteoclast progenitors. Cancer Cell 20(6):701–714
Luzzi KJ, MacDonald IC, Schmidt EE, Kerkvliet N, Morris VL, Chambers AF et al (1998) Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am J Pathol 153(3):865–873
Ma J, Lin JY, Alloo A, Wilson BJ, Schatton T, Zhan Q et al (2010) Isolation of tumorigenic circulating melanoma cells. Biochem Biophys Res Commun 402(4):711–717
Malanchi I, Santamaria-Martínez A, Susanto E, Peng H, Lehr HA, Delaloye JF et al (2011) Interactions between cancer stem cells and their niche govern metastatic colonization. Nature 481(7379):85–89
Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY et al (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704–715
Manthey CL, Johnson DL, Illig CR, Tuman RW, Zhou Z, Baker JF et al (2009) JNJ-28312141, a novel orally active colony-stimulating factor-1 receptor/FMS-related receptor tyrosine kinase-3 receptor tyrosine kinase inhibitor with potential utility in solid tumors, bone metastases, and acute myeloid leukemia. Mol Cancer Ther 8(11):3151–3161
Martin SS, Ridgeway AG, Pinkas J, Lu Y, Reginato MJ, Koh EY et al (2004) A cytoskeleton-based functional genetic screen identifies Bcl-xL as an enhancer of metastasis, but not primary tumor growth. Oncogene 23(26):4641–4645
Martin FT, Dwyer RM, Kelly J, Khan S, Murphy JM, Curran C et al (2010) Potential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: stimulation of epithelial to mesenchymal transition (EMT). Breast Cancer Res Treat 2:317–326
Massard C, Deutsch E, Soria JC (2006) Tumour stem cell-targeted treatment: elimination or differentiation. Ann Oncol 17:1620–1624
Masson V, de la Ballina LR, Munaut C, Wielockx B, Jost M, Maillard C et al (2005) Contribution of host MMP-2 and MMP-9 to promote tumor vascularization and invasion of malignant keratinocytes. FASEB J 19(2):234–236
Matsusue R, Kubo H, Hisamori S, Okoshi K, Takagi H, Hida K et al (2009) Hepatic stellate cells promote liver metastasis of colon cancer cells by the action of SDF-1/CXCR4 axis. Ann Surg Oncol 16(9):2645–2653
McGowan PM, Simedrea C, Ribot EJ, Foster PJ, Palmieri D, Steeg PS et al (2011) Notch1 inhibition alters the CD44hi/CD24lo population and reduces the formation of brain metastases from breast cancer. Mol Cancer Res 9:834–844
Medema JP, Vermeulen L (2011) Microenvironmental regulation of stem cells in intestinal homeostasis and cancer. Nature 474(7351):318–326
Mego M, Mani SA, Lee BN, Li C, Evans KW, Cohen EN et al (2012a) Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: The effect of neoadjuvant therapy. Int J Cancer 130(4):808–816
Mego M, Gao H, Lee BN, Cohen EN, Tin S, Giordano A et al (2012b) Prognostic value of EMT-circulating tumor cells in metastatic breast cancer patients undergoing high-dose chemotherapy with autologous hematopoietic stem cell transplantation. J Cancer Educ 3:369–380
Méhes G, Witt A, Kubista E, Ambros PF (2001) Circulating breast cancer cells are frequently apoptotic. Am J Pathol 159(1):17–20
Mehlen P, Puisieux A (2006) Metastasis: a question of life or death. Nat Rev Cancer 6(6):449–458
Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ, Huth JF et al (2004) Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 10(24):8152–8162
Meng Y, Beckett MA, Liang H, Mauceri HJ, Nv R, Cohen KS et al (2010) Blockade of tumor necrosis factor a signaling in tumor-associated macrophages as a radiosensitizing strategy. Cancer Res 70:1534–1543
Minn AJ, Kang Y, Serganova I, Gupta GP, Giri DD, Doubrovin M et al (2005a) Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J Clin Invest 115(1):44–55
Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD et al (2005b) Genes that mediate breast cancer metastasis to lung. Nature 436(7050):518–524
Mitra SK, Hanson DA, Schlaepfer DD (2005) Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol 6(1):56–68
Mizutani K, Sud S, McGregor NA, Martinovski G, Rice BT, Craig MJ et al (2009) The chemokine CCL2 increases prostate tumor growth and bone metastasis through macrophage and osteoclast recruitment. Neoplasia 11(11):1235–1242
Moitra K, Lou H, Dean M (2011) Multidrug efflux pumps and cancer stem cells: insights into multidrug resistance and therapeutic development. Clin Pharmacol Ther 89(4):491–502
Monteiro J, Fodde R (2010) Cancer stemness and metastasis: therapeutic consequences and perspectives. Eur J Cancer 46(7):1198–1203
Moore KA, Lemischka IR (2006) Stem cells and their niches. Science 311(5769):1880–1885
Morel AP, Lièvre M, Thomas C, Hinkal G, Ansieau S, Puisieux A (2008) Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 3(8):e2888
Morikawa K, Walker SM, Nakajima M, Pathak S, Jessup JM, Fidler IJ (1988) Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice. Cancer Res 48(23):6863–6871
Morrison SJ, Spradling AC (2008) Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell 132(4):598–611
Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME et al (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410(6824):50–56
Müller V, Stahmann N, Riethdorf S, Rau T, Zabel T, Goetz A et al (2005) Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity. Clin Cancer Res 11(10):3678–3685
Mundy GR (2002) Metastasis to bone: causes, consequences therapeutic opportunities. Nat Rev Cancer 2:584–593
Murdoch C, Lewis CE (2005) Macrophage migration and gene expression in response to tumor hypoxia. Int J Cancer 117(5):701–708
Nagai T, Tanaka M, Tsuneyoshi Y, Xu B, Michie SA, Hasui K et al (2009) Targeting tumor-associated macrophages in an experimental glioma model with a recombinant immunotoxin to folate receptor beta. Cancer Immunol Immunother 58(10):1577–1586
Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L et al (2007) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450(7173):1235–1239
Nash GF, Turner LF, Scully MF, Kakkar AK (2002) Platelets and cancer. Lancet Oncol 3(7):425–430
Naumov GN, MacDonald IC, Weinmeister PM, Kerkvliet N, Nadkarni KV, Wilson SM et al (2002) Persistence of solitary mammary carcinoma cells in a secondary site: a possible contributor to dormancy. Cancer Res 62(7):2162–2218
Nervi B, Ramirez P, Rettig MP, Uy GL, Holt MS, Ritchey JK et al (2009) Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100. Blood 113:6206–6214
Nguyen DX, Massagué J (2007) Genetic determinants of cancer metastasis. Nat Rev Genet 8:341–352
Nguyen DX, Bos PD, Massagué J (2009) Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer 9(4):274–284
Nguyen LV, Vanner R, Dirks P, Eaves CJ (2012) Cancer stem cells: an evolving concept. Nat Rev Cancer 12:133–143
Nieto MA (2013) Epithelial plasticity: a common theme in embryonic and cancer cells. Science 342(6159):1234850
Norton L, Massagué J (2006) Is cancer a disease of self-seeding? Nat Med 12(8):875–878
O’Boyle G, Swidenbank I, Marshall H, Barker CE, Armstrong J, White SA et al (2013) Inhibition of CXCR4-CXCL12 chemotaxis in melanoma by AMD11070. Br J Cancer 108(8):1634–1640
O’Connell JT, Sugimoto H, Cooke VG, MacDonald BA, Mehta AI, LeBleu VS et al (2011) VEGF-A and Tenascin-C produced by S100A4+ stromal cells are important for metastatic colonization. Proc Natl Acad Sci U S A 108(38):16002–16007
O’Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS et al (1997) Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88(2):277–285
Oka H, Shiozaki H, Kobayashi K, Inoue M, Tahara H, Kobayashi T et al (1993) Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res 53(7):1696–1701
Oltean S, Sorg BS, Albrecht T, Bonano VI, Brazas RM, Dewhirst MW et al (2006) Alternative inclusion of fibroblast growth factor receptor 2 exon IIIc in Dunning prostate tumors reveals unexpected epithelial mesenchymal plasticity. Proc Natl Acad Sci U S A 141103(38):14116–14121
Oskarsson T, Massagué J (2012) Extracellular matrix players in metastatic niches. EMBO J 31(2):254–256
Oskarsson T, Acharyya S, Zhang XH, Vanharanta S, Tavazoie SF, Morris PG et al (2011) Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nat Med 17(7):867–874
Pàez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Viñals F et al (2009) Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15(3):220–231
Pajonk F, Vlashi E, McBride WH (2010) Radiation resistance of cancer stem cells: the 4 R’s of radiobiology revisited. Stem Cells 28(4):639–648
Palafox M, Ferrer I, Pellegrini P, Vila S, Hernandez-Ortega S, Urruticoechea A et al (2012) RANK induces epithelial-mesenchymal transition and stemness in human mammary epithelial cells and promotes tumorigenesis and metastasis. Cancer Res 72(11):2879–2888
Pallini R, Ricci-Vitiani L, Banna GL, Signore M, Lombardi D, Todaro M et al (2008) Cancer stem cell analysis and clinical outcome in patients with glioblastoma multiforme. Clin Cancer Res 14(24):8205–8212
Pantel K, Alix-Panabières C (2007) The clinical significance of circulating tumor cells. Nat Clin Pract Oncol 4(2):62–63
Pardal R, Clarke MF, Morrison SJ (2003) Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 3(12):895–902
Park Y, Gerson SL (2005) DNA repair defects in stem cell function and aging. Annu Rev Med 56:495–508
Pasqualini R, Koivunen E, Kain R, Lahdenranta J, Sakamoto M, Stryhn A et al (2000) Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Res 60(3):722–727
Paulus P, Stanley ER, Schafer R, Abraham D, Aharinejad S (2006) Colony-stimulating factor-1 antibody reverses chemoresistance in human MCF-7 breast cancer xenografts. Cancer Res 66:4349–4356
Peinado H, Alečković M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G et al (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18(6):883–891
Peter ME (2010) Regulating cancer stem cells the miR way. Cell Stem Cell 6(1):4–6
Piccirillo SG, Reynolds BA, Zanetti N, Lamorte G, Binda E, Broggi G et al (2006) Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 444:761–765
Piotrowicz RS, Damaj BB, Hachicha M, Incardona F, Howell SB, Finlayson M (2011) A6 peptide activates CD44 adhesive activity, induces FAK and MEK phosphorylation, and inhibits the migration and metastasis of CD44-expressing cells. Mol Cancer Ther 10:2072–2082
Playford MP, Schaller MD (2004) The interplay between Src and integrins in normal and tumor biology. Oncogene 48:7928–7946
Podsypanina K, Du YC, Jechlinger M, Beverly LJ, Hambardzumyan D, Varmus H (2008) Seeding and propagation of untransformed mouse mammary cells in the lung. Science 321(5897):1841–1844
Potten CS, Owen G, Booth D (2002) Intestinal stem cells protect their genome by selective segregation of template DNA strands. J Cell Sci 115(11):2381–2388
Price DJ, Miralem T, Jiang S, Steinberg R, Avraham H (2001) Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells. Cell Growth Differ 12(3):129–135
Psaila B, Lyden D (2009) The metastatic niche: adapting the foreign soil. Nat Rev Cancer 9(4):285–293
Puig-Kröger A, Sierra-Filardi E, Domínguez-Soto A, Samaniego R, Corcuera MT, Gómez-Aguado F et al (2009) Folate receptor beta is expressed by tumor-associated macrophages and constitutes a marker for M2 anti-inflammatory/regulatory macrophages. Cancer Res 69(24):9395–9403
Pulaski HL, Spahlinger G, Silva IA, McLean K, Kueck AS, Reynolds RK et al (2009) Identifying alemtuzumab as an anti-myeloid cell antiangiogenic therapy for the treatment of ovarian cancer. J Transl Med 7:49
Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR et al (2011) CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475(7355):222–225
Radinsky R (1991) Growth factors and their receptors in metastasis. Semin Cancer Biol 2(3):169–177
Radinsky R, Risin S, Fan D, Dong Z, Bielenberg D, Bucana CD et al (1995) Level and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cells. Clin Cancer Res 1(1):19–31
Radisky DC, LaBarge MA (2008) Epithelial-mesenchymal transition and the stem cell phenotype. Cell Stem Cell 2(6):511–512
Raimondi C, Gradilone A, Naso G, Vincenzi B, Petracca A, Nicolazzo C et al (2011) Epithelial-mesenchymal transition and stemness features in circulating tumor cells from breast cancer patients. Breast Cancer Res Treat 130(2):449–455
Ramsey DM, McAlpine SR (2013) Halting metastasis through CXCR4 inhibition. Bioorg Med Chem Lett 23(1):20–25
Rappa G, Fodstad O, Lorico A (2008) The stem cell-associated antigen CD133 (Prominin-1) is a molecular therapeutic target for metastatic melanoma. Stem Cells 26:3008–3017
Rattigan Y, Hsu JM, Mishra PJ, Glod J, Banerjee D (2010) Interleukin 6 mediated recruitment of mesenchymal stem cells to the hypoxic tumor milieu. Exp Cell Res 316(20):3417–3424
Redjal N, Chan JA, Segal RA, Kung AL (2006) CXCR4 inhibition synergizes with cytotoxic chemotherapy in gliomas. Clin Cancer Res 12(22):6765–6771
Reya T, Clevers H (2005) Wnt signalling in stem cells and cancer. Nature 434(7035):843–850
Reynolds TY, Rockwell S, Glazer PM (1996) Genetic instability induced by the tumor microenvironment. Cancer Res 56(24):5754–5757
Rich JN (2007) Cancer stem cells in radiation resistance. Cancer Res 67(19):8980–8984
Riechelmann H, Sauter A, Golze W, Hanft G, Schroen C, Hoermann K et al (2008) Phase I trial with the CD44v6-targeting immunoconjugate bivatuzumab mertansine in head and neck squamous cell carcinoma. Oral Oncol 44:823–829
Roca H, Varsos ZS, Sud S, Craig MJ, Ying C, Pienta KJ (2009) CCL2 and interleukin-6 promote survival of human CD11b+ peripheral blood mononuclear cells and induce M2-type macrophage polarization. J Biol Chem 284:34342–34354
Rohwedel J, Guan K, Wobus AM (1999) Induction of cellular differentiation by retinoic acid in vitro. Cells Tissues Organs 165:190–202
Roland CL, Dineen SP, Lynn KD, Sullivan LA, Dellinger MT, Sadegh L et al (2009) Inhibition of vascular endothelial growth factor reduces angiogenesis and modulates immune cell infiltration of orthotopic breast cancer xenografts. Mol Cancer Ther 8(7):1761–1771
Ross AA, Cooper BW, Lazarus HM, Mackay W, Moss TJ, Ciobanu N et al (1993) Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques. Blood 82(9):2605–2610
Rudnick JA, Arendt LM, Klebba I, Hinds JW, Iyer V, Gupta PB et al (2011) Functional heterogeneity of breast fibroblasts is defined by a prostaglandin secretory phenotype that promotes expansion of cancer-stem like cells. PLoS One 6(9), e24605
Ruoslahti E (1994–1995) Fibronectin and its alpha 5 beta 1 integrin receptor in malignancy. Invasion Metastasis 14(1–6):87–97
Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M et al (2011) Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469(7330):415–418
Sceneay J, Smyth MJ, Moller A (2013) The pre-metastatic niche: finding common ground. Cancer Metastasis Rev 32:449–464
Schardt JA, Meyer M, Hartmann CH, Schubert F, Schmidt-Kittler O, Fuhrmann C et al (2005) Genomic analysis of single cytokeratin-positive cells from bone marrow reveals early mutational events in breast cancer. Cancer Cell 8(3):227–239
Schewe DM, Aguirre-Ghiso JA (2009) Inhibition of eIF2α dephosphorylation maximizes bortezomib efficiency and eliminates quiescent multiple myeloma cells surviving proteasome inhibitor therapy. Cancer Res 69:1545–1552
Schmidt-Kittler O, Ragg T, Daskalakis A, Granzow M, Ahr A, Blankenstein TJ et al (2003) From latent disseminated cells to overt metastasis: genetic analysis of systemic breast cancer progression. Proc Natl Acad Sci U S A 100(13):7737–7742
Schröder C, Schumacher U, Fogel M, Feuerhake F, Müller V, Wirtz RM et al (2009) Expression and prognostic value of L1-CAM in breast cancer. Oncol Rep 22(5):1109–1117
Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219(4587):983–985
Seton-Rogers S (2011) Cancer stem cells. VEGF promotes stemness. Nat Rev Cancer 11(12):831
Shao R, Bao S, Bai X, Blanchette C, Anderson RM, Dang T et al (2004) Acquired expression of periostin by human breast cancers promotes tumor angiogenesis through up-regulation of vascular endothelial growth factor receptor 2 expression. Mol Cell Biol 9:3992–4003
Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S et al (2010) A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 141(1):69–80
Shi X, Zhang Y, Zheng J, Pan J (2012) Reactive oxygen species in cancer stem cells. Antioxid Redox Signal 16(11):1215–1228
Shien K, Toyooka S, Ichimura K, Soh J, Furukawa M, Maki Y et al (2012) Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy. Lung Cancer 77(1):162–167
Shiozawa Y, Pedersen EA, Havens AM, Jung Y, Mishra A, Joseph J et al (2011) Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest 121(4):1298–1312
Shiozawa Y, Nie B, Pienta KJ, Morgan TM, Taichman RS (2013) Cancer stem cells and their role in metastasis. Pharmacol Ther 138(2):285–293
Sica A, Bronte V (2007) Altered macrophage differentiation and immune dysfunction in tumor development. J Clin Invest 117:1155–1166
Sica A, Larghi P, Mancino A, Rubino L, Porta C, Totaro MG et al (2008) Macrophage polarization in tumour progression. Semin Cancer Biol 18(5):349–355
Sinha P, Clements VK, Ostrand-Rosenberg S (2005) Reduction of myeloid-derived suppressor cells and induction of M1 macrophages facilitate the rejection of established metastatic disease. J Immunol 174:636–645
Sleeman JP, Nazarenko I, Thiele W (2011) Do all roads lead to Rome? Routes to metastasis development. Int J Cancer 128(11):2511–2526
Smith MC, Luker KE, Garbow JR, Prior JL, Jackson E, Piwnica-Worms D et al (2004) CXCR4 regulates growth of both primary and metastatic breast cancer. Cancer Res 64(23):8604–8612
Sneddon JB (2007) The cancer stem cell niche. Cell Stem Cell 1:607–661
Soeda A, Park M, Lee D, Lee D, Mintz A, Androutsellis-Theotokis A et al (2009) Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha. Oncogene 28(45):3949–3959
Solinas G, Germano G, Mantovani A, Allavena P (2009) Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol 86:1065–1073
Sosa MS, Bragado P, Aguirre-Ghiso JA (2014) Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat Rev Cancer 14(9):611–622
Steeg PS (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12(8):895–904
Stott SL, Hsu CH, Tsukrov DI, Yu M, Miyamoto DT, Waltman BA et al (2010) Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proc Natl Acad Sci U S A 107(43):18392–18397
Stupack DG, Teitz T, Potter MD, Mikolon D, Houghton PJ, Kidd VJ et al (2006) Potentiation of neuroblastoma metastasis by loss of caspase-8. Nature 439(7072):95–99
Sun YX, Fang M, Wang J, Cooper CR, Pienta KJ, Taichman RS (2007) Expression and activation of alpha v beta 3 integrins by SDF-1/CXC12 increases the aggressiveness of prostate cancer cells. Prostate 67(1):61–73
Sun P, Xia S, Lal B, Eberhart CG, Quinones-Hinojosa A, Maciaczyk J et al (2009) DNER, an epigenetically modulated gene, regulates glioblastoma-derived neurosphere cell differentiation and tumor propagation. Stem Cells 27(7):1473–1486
Takahashi Y, Mai M (2005) Antibody against vascular endothelial growth factor (VEGF) inhibits angiogenic switch and liver metastasis in orthotopic xenograft model with site-dependent expression of VEGF. J Exp Clin Cancer Res 24(2):237–243
Takebe N, Harris PJ, Warren RQ, Ivy SP (2011) Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nat Rev Clin Oncol 8:97–106
Tanaka K, Hiraiwa N, Hashimoto H, Yamazaki Y, Kusakabe M (2004) Tenascin-C regulates angiogenesis in tumor through the regulation of vascular endothelial growth factor expression. Int J Cancer 108:31–40
Tang X, Mo C, Wang Y, Wei D, Xiao H (2013) Anti-tumour strategies aiming to target tumour-associated macrophages. Immunology 138(2):93–104
Tate CR, Rhodes LV, Segar HC, Driver JL, Pounder FN, Burow ME (2012) Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat. Breast Cancer Res 14:R79
Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD et al (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451(7175):147–152
Terranova VP, Williams JE, Liotta LA, Martin GR (1984) Modulation of the metastatic activity of melanoma cells by laminin and fibronectin. Science 226(4677):982–985
Theodoropoulos PA, Polioudaki H, Agelaki S, Kallergi G, Saridaki Z, Mavroudis D et al (2010) Circulating tumor cells with a putative stem cell phenotype in peripheral blood of patients with breast cancer. Cancer Lett 288:99–106
Tokes AM, Hortovanyi E, Kulka J, Jackel M, Kerenyi T, Kadar A (1999) Tenascin expression and angiogenesis in breast cancers. Pathol Res Pract 195:821–828
Tonini T, Rossi F, Claudio PP (2003) Molecular basis of angiogenesis and cancer. Oncogene 22:6549–6556
Townson JL, Chambers AF (2006) Dormancy of solitary metastatic cells. Cell Cycle 5(16):1744–1750
Tsagozis P, Eriksson F, Pisa P (2008) Zoledronic acid modulates antitumoral responses of prostate cancer-tumor associated macrophages. Cancer Immunol Immunother 57:1451–1459
Tsai HC, Li H, Van Neste L, Cai Y, Robert C, Rassool FV et al (2012) Transient low doses of DNA-demethylating agents exert durable antitumor effects on hematological and epithelial tumor cells. Cancer Cell 21(3):430–446
Tsuji T, Ibaragi S, Shima K, Hu MG, Katsurano M, Sasaki A et al (2008) Epithelial-mesenchymal transition induced by growth suppressor p12CDK2-AP1 promotes tumor cell local invasion but suppresses distant colony growth. Cancer Res 68(24):10377–10386
Tsuji T, Ibaragi S, Hu GF (2009) Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Res 69(18):7135–7139
Tyagi A, Singh RP, Ramasamy K, Raina K, Redente EF, Dwyer-Nield LD et al (2009) Growth inhibition and regression of lung tumors by silibinin: modulation of angiogenesis by macrophage-associated cytokines and nuclear factor-kappaB and signal transducers and activators of transcription 3. Cancer Prev Res 2(1):74–83
Valiente M, Obenauf AC, Jin X, Chen Q, Zhang XH, Lee DJ et al (2014) Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell 156(5):1002–1016
Van Ginderachter JA, Movahedi K, Van den Bossche J, De Baetselier P (2008) Macrophages, PPARs, and Cancer. PPAR Res 2008:169414
van Moorselaar RJ, Voest EE (2002) Angiogenesis in prostate cancer: its role in disease progression and possible therapeutic approaches. Mol Cell Endocrinol 197(1-2):239–250
Veltman JD, Lambers MEH, van Nimwegen M, Hendriks RW, Hoogsteden HC, Hegmans JP et al (2010) Zoledronic acid impairs myeloid differentiation to tumour associated macrophages in mesothelioma. Br J Cancer 103:629–641
Vermeulen L, de Sousa E, Melo F, van der Heijden M, Cameron K, de Jong JH et al (2010) Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol 12(5):468–476
Vincan E, Brabletz T, Faux MC, Ramsay RG (2007) A human three-dimensional cell line model allows the study of dynamic and reversible epithelial-mesenchymal and mesenchymal-epithelial transition that underpins colorectal carcinogenesis. Cells Tissues Organs 185(1-3):20–28
Vishvakarma NK, Singh SM (2010) Immunopotentiating effect of proton pump inhibitor pantoprazole in a lymphoma-bearing murine host: implication in antitumor activation of tumor-associated macrophages. Immunol Lett 134:83–92
Von Holst A (2008) Tenascin C in stem cell niches: redundant, permissive or instructive? Cells Tissues Organs 188(1-2):170–177
Wang H, Fu W, Im JH, Zhou Z, Santoro SA, Iyer V et al (2004) Tumor cell alpha3beta1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis. J Cell Biol 164(6):935–941
Wang Q, Chen ZG, Du CZ, Wang HW, Yan L, Gu J (2009) Cancer stem cell marker CD133+ tumour cells and clinical outcome in rectal cancer. Histopathology 55(3):284–293
Welford AF, Biziato D, Coffelt SB, Nucera S, Fisher M, Pucci F et al (2011) TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice. J Clin Invest 121(5):1969–1973
Wels J, Kaplan RN, Rafii S, Lyden D (2008) Migratory neighbors and distant invaders: tumor-associated niche cells. Genes Dev 22(5):559–574
Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT et al (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10:145–147
Wu KJ (2011) Direct activation of Bmi1 by Twist1: implications in cancer stemness, epithelial-mesenchymal transition, and clinical significance. Chang Gung Med J 34(3):229–238
Wu Y, Wu PY (2009) CD133 as a marker for cancer stem cells: progresses and concerns. Stem Cells Dev 18:1127–1134
Wu KJ, Yang MH (2011) Epithelial-mesenchymal transition and cancer stemness: the Twist1-Bmi1 connection. Biosci Rep 31(6):449–455
Xin H, Zhang C, Herrmann A, Du Y, Figlin R, Yu H (2009) Sunitinib inhibition of STAT3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells. Cancer Res 69:2506–2513
Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B et al (2010) Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467(7319):1114–1117
Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C et al (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117(7):927–939
Yang MH, Wu MZ, Chiou SH, Chen PM, Chang SY, Liu CJ et al (2008) Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol 10(3):295–305
Yao D, Dai C, Peng S (2011) Mechanism of the mesenchymal-epithelial transition and its relationship with metastatic tumor formation. Mol Cancer Res 9(12):1608–1620
Yates CC, Shepard CR, Stolz DB, Wells A (2007) Co-culturing human prostate carcinoma cells with hepatocytes leads to increased expression of E-cadherin. Br J Cancer 96(8):1246–1252
Yin JJ, Selander K, Chirgwin JM, Dallas M, Grubbs BG, Wieser R et al (1999) TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J Clin Invest 103(2):197–206
Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT et al (2013) Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339(6119):580–584
Yu H, Lee H, Herrmann A, Buettner R, Jove R (2014) Revisiting STAT3 signalling in cancer: new and unexpected biological functions. Nat Rev Cancer 14(11):736–746
Zarrilli R, Bruni CB, Riccio A (1994) Multiple levels of control of insulin-like growth factor gene expression. Mol Cell Endocrinol 101(1-2):R1–R14
Zeisberger SM, Odermatt B, Marty C, Zehnder-Fjallman AHM, Ballmer-Hofer K, Schwendener RA (2006) Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach. Br J Cancer 95:272–281
Zeng Z, Samudio IJ, Munsell M, An J, Huang Z, Estey E et al (2006) Inhibition of CXCR4 with the novel RCP168 peptide overcomes stroma-mediated chemoresistance in chronic and acute leukemias. Mol Cancer Ther 5(12):3113–3121
Zhan M, Zhao H, Han ZC (2004) Signalling mechanisms of anoikis. Histol Histopathol 19(3):973–983
Zhang JW, Niu C, Ye L, Huang HY, He X, Tong WG et al (2003) Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425:836–841
Zhang XH, Wang Q, Gerald W, Hudis CA, Norton L, Smid M et al (2009) Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell 16(1):67–78
Zhang W, Zhu XD, Sun HC, Xiong YQ, Zhuang PY, Xu HX et al (2010) Depletion of tumor-associated macrophages enhances the effect of sorafenib in metastatic liver cancer models by antimetastatic and antiangiogenic effects. Clin Cancer Res 16(13):3420–3430
Zhang XH, Jin X, Malladi S, Zou Y, Wen YH, Brogi E et al (2013) Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma. Cell 154(5):1060–1073
Zhao P, Li Y, Lu Y (2010) Aberrant expression of CD133 protein correlates with Ki-67 expression and is a prognostic marker in gastric adenocarcinoma. BMC Cancer 10:218
Zhu J, Emerson SG (2004) A new bone to pick: osteoblasts and the haematopoietic stem-cell niche. Bioessays 26(6):595–599
Zhu XD, Zhang JB, Zhuang PY, Zhu HG, Zhang W, Xiong YQ et al (2008) High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. J Clin Oncol 26(16):2707–2716
Zhu X, Fujita M, Snyder L, Okada H (2010) Systemic delivery of neutralizing antibody targeting CCL2 for glioma therapy. J Neurooncol 104:83–92
Zlotnik A, Burkhardt AM, Homey B (2011) Homeostatic chemokine receptors and organ-specific metastasis. Nat Rev Immunol 11(9):597–606
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Ferrari, P., Nicolini, A. (2015). Cellular Plasticity, Cancer Stem Cells and Metastasis. In: Babashah, S. (eds) Cancer Stem Cells: Emerging Concepts and Future Perspectives in Translational Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-21030-8_2
Download citation
DOI: https://doi.org/10.1007/978-3-319-21030-8_2
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-21029-2
Online ISBN: 978-3-319-21030-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)