Advertisement

Cancer Stem Cells in Metastasis Therapy

  • Esra Aydemir Çoban
  • Fikrettin Şahin
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1089)

Abstract

Tumors consists of subpopulation of cells in which each subtype has contributes to tumor progression. Specifically one subtype known as cancer stem cells are associated with the initiation, progression, resistance to conventional therapies and metastasis. Metastasis is leading cause of cancer related deaths. Overall it is important to consider cancer as a whole in which a mutated cell proliferating indefinitely and forming its hierarchy consisting of subgroups with different molecular signatures. To be able to target this disease we need to evaluate every step including initiation, progression, survival, angiogenesis and finally migration and repopulation. Cancer stem cells do play vital roles in each step however when metastasis can be stopped or eliminated we talk about saving a life or improving its quality. Considering how deeply these cancer stem like cells affect the tumor life and metastasis it is crucial to develop effective strategies against them. Metastatic cascade can also be directed by membrane derived vesicles specifically exosomes. Several studies show the role of exosomes in mediating cellular migration and pre-metastatic niche formation. During this chapter we wanted to explain in detail how the metastasis occur in tumor and how cancer stem cells contribute into the development of metastatic cascade and possibly suggest therapeutic approaches against cancer stem cells.

Keywords

Cancer stem cells Metastasis Cancer therapy 

Abbreviations

CSCs

cancer stem cells

MMPs

matrix metalloproteinases

EMT

epithelial-to-mesenchymal transition

ALDH1A1

Aldehyde Dehydrogenase 1 Family Member A1

RTKs

receptor tyrosine kinases

MICs

metastasis-initiating cells

TICs

tumor-initiating cells

hWAPL

human wings apart-like

HPV

human papillomavirus

Pdcd4

programmed cell death protein 4

CXCL12

chemokine stromal cell-derived factor 1

VEGFR-1

vascular endothelial growth factor receptor 1

CDs

cluster of differentiation

CXCR4

chemokine receptor complex 4

CAFs

cancer associated fibroblasts

IGF-1

insuling growth factor 1

IL-17A

interleukin 17A

DTC

disseminated tumor cell

MIF

migration inhibitory factor

RARRES3

Retinoic Acid Receptor Responder 3

NKX2-1

homeobox domain-containing transcription

MITF

microphthalmia-associated transcription factor

EVs

Extracellular vesicles

ABs

apoptotic bodies

References

  1. Achilles EG, Fernandez A, Allred EN, Kisker O, Udagawa T, Beecken WD, Flynn E, Folkman J (2001) Heterogeneity of angiogenic activity in a human liposarcoma: a proposed mechanism for “no take” of human tumors in mice. J Natl Cancer Inst 93(14):1075–1081.  https://doi.org/10.1093/jnci/93.14.1075CrossRefPubMedGoogle Scholar
  2. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100(7):3983–3988.  https://doi.org/10.1073/pnas.0530291100CrossRefPubMedPubMedCentralGoogle Scholar
  3. Andermarcher E, Surani MA, Gherardi E (1996) Co-expression of the HGF/SF and c-met genes during early mouse embryogenesis precedes reciprocal expression in adjacent tissues during organogenesis. Dev Genet 18(3):254–266.  https://doi.org/10.1002/(Sici)1520-6408(1996)18:3<254::Aid-Dvg6>3.0.Co;2-8CrossRefPubMedGoogle Scholar
  4. Asangani IA, Rasheed SAK, Nikolova DA, Leupold JH, Colburn NH, Post S, Allgayer H (2008) MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27(15):2128–2136.  https://doi.org/10.1038/sj.onc.1210856CrossRefPubMedGoogle Scholar
  5. Aydemir E, Bayrak OF, Sahin F, Atalay B, Kose GT, Ozen M, Sevli S, Dalan AB, Yalvac ME, Dogruluk T, Ture U (2012) Characterization of cancer stem-like cells in chordoma. J Neurosurg 116(4):810–820.  https://doi.org/10.3171/2011.12.JNS11430CrossRefPubMedGoogle Scholar
  6. Bao SD, Wu QL, McLendon RE, Hao YL, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444(7120):756–760.  https://doi.org/10.1038/nature05236CrossRefPubMedGoogle Scholar
  7. Barros EGD, Palumbo A, Mello PLP, de Mattos RM, da Silva JH, Pontes B, Viana NB, do Amaral RF, FRS L, da Costa NM, Palmero CY, Miranda-Alves L, Takiya CM, Nasciutti LE (2014) The reciprocal interactions between astrocytes and prostate cancer cells represent an early event associated with brain metastasis. Clin Exp Metastas 31(4):461–474.  https://doi.org/10.1007/s10585-014-9640-yCrossRefGoogle Scholar
  8. Bellizzi A, Sebastian S, Ceglia P, Centonze M, Divella R, Manzillo EF, Azzariti A, Silvestris N, Montemurro S, Caliandro C, De Luca R, Cicero G, Rizzo S, Russo A, Quaranta M, Simone G, Paradiso A (2013) Co-expression of CD133(+)/CD44(+) in human colon cancer and liver metastasis. J Cell Physiol 228(2):408–415.  https://doi.org/10.1002/jcp.24145CrossRefPubMedGoogle Scholar
  9. Bladt F, Riethmacher D, Isenmann S, Aguzzi A, Birchmeier C (1995) Essential role for the C-met receptor in the migration of myogenic precursor cells into the limb bud. Nature 376(6543):768–771.  https://doi.org/10.1038/376768a0CrossRefPubMedGoogle Scholar
  10. Boccaccio C, Gaudino G, Gambarotta G, Galimi F, Comoglio PM (1994) Hepatocyte growth-factor (Hgf) receptor expression is inducible and is part of the delayed-early response to Hgf. J Biol Chem 269(17):12846–12851PubMedGoogle Scholar
  11. Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3(7):730–737CrossRefGoogle Scholar
  12. 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.  https://doi.org/10.1038/nrc1694CrossRefPubMedGoogle Scholar
  13. Budczies J, von Winterfeld M, Klauschen F, Bockmayr M, Lennerz JK, Denkert C, Wolf T, Warth A, Dietel M, Anagnostopoulos I, Weichert W, Wittschieber D, Stenzinger A (2015) The landscape of metastatic progression patterns across major human cancers. Oncotarget 6(1):570–583.  https://doi.org/10.18632/oncotarget.2677CrossRefPubMedGoogle Scholar
  14. Cabrera MC, Hollingsworth RE, Hurt EM (2015) Cancer stem cell plasticity and tumor hierarchy. World J Stem Cells 7(1):27–36.  https://doi.org/10.4252/wjsc.v7.i1.27CrossRefPubMedPubMedCentralGoogle Scholar
  15. Camussi G, Quesenberry PJ (2013) Perspectives on the potential therapeutic uses of vesicles. Exosomes Microvesicles 1(6).  https://doi.org/10.5772/57393
  16. Cao Y, Slaney CY, Bidwell BN, Parker BS, Johnstone CN, Rautela J, Eckhardt BL, Anderson RL (2014) BMP4 inhibits breast cancer metastasis by blocking myeloid-derived suppressor cell activity. Cancer Res 74(18):5091–5102.  https://doi.org/10.1158/0008-5472.Can-13-3171CrossRefPubMedGoogle Scholar
  17. Celia-Terrassa T, Kang YB (2016) Distinctive properties of metastasis-initiating cells. Genes Dev 30(8):892–908.  https://doi.org/10.1101/gad.277681.116CrossRefPubMedPubMedCentralGoogle Scholar
  18. Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2(8):563–572.  https://doi.org/10.1038/nrc865CrossRefGoogle Scholar
  19. Chan KS, Espinosa I, Chao M, Wong D, Ailles L, Diehn M, Gill H, Presti J, Chang HY, van de Rijn M, Shortliffe L, Weissman IL (2009) Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells. Proc Natl Acad Sci U S A 106(33):14016–14021.  https://doi.org/10.1073/pnas.0906549106CrossRefPubMedPubMedCentralGoogle Scholar
  20. Chay CH, Cooper CR, Gendernalik JD, Dhanasekaran SM, Chinnaiyan AM, Rubin MA, Schmaier AH, Pienta KJ (2002) A functional thrombin receptor (PAR1) is expressed on bone-derived prostate cancer cell lines. Urology 60(5):760–765.  https://doi.org/10.1016/S0090-4295(02)01969-6CrossRefPubMedGoogle Scholar
  21. Cheli Y, Giuliano S, Fenouille N, Allegra M, Hofman V, Hofman P, Bahadoran P, Lacour JP, Tartare-Deckert S, Bertolotto C, Ballotti R (2011) Hypoxia and MITF control metastatic behaviour in mouse and human melanoma cells. Pigment Cell Melanoma Res 24(4):799–799Google Scholar
  22. Chen W, Dong J, Haiech J, Kilhoffer MC, Zeniou M (2016) Cancer stem cell quiescence and plasticity as major challenges in cancer therapy. Stem Cells Int.  https://doi.org/10.1155/2016/1740936
  23. Cheung WKC, Zhao MH, Liu ZZ, Stevens LE, Cao PD, Fang JE, Westbrook TF, Nguyen DX (2013) Control of alveolar differentiation by the lineage transcription factors GATA6 and HOPX inhibits lung adenocarcinoma metastasis. Cancer Cell 23(6):725–738.  https://doi.org/10.1016/j.ccr.2013.04.009CrossRefPubMedPubMedCentralGoogle Scholar
  24. Chu P, Clanton DJ, Snipas TS, Lee J, Mitchell E, Nguyen ML, Hare E, Peach RJ (2009) Characterization of a subpopulation of colon cancer cells with stem cell-like properties. Int J Cancer 124(6):1312–1321.  https://doi.org/10.1002/ijc.24061CrossRefPubMedGoogle Scholar
  25. Cooper CR, Chay CH, Gendernalik JD, Lee HL, Bhatia J, Taichman RS, McCauley LK, Keller ET, Pienta KJ (2003) Stromal factors involved in prostate carcinoma metastasis to bone. Cancer 97(3):739–747.  https://doi.org/10.1002/cncr.11181CrossRefPubMedGoogle Scholar
  26. Croker AK, Allan AL (2008) Cancer stem cells: implications for the progression and treatment of metastatic disease. J Cell Mol Med 12(2):374–390.  https://doi.org/10.1111/j.1582-4934.2007.00211.xCrossRefPubMedGoogle Scholar
  27. Croker AK, Goodale D, Chu J, Postenka C, Hedley BD, Hess DA, Allan AL (2009) High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. J Cell Mol Med 13(8b):2236–2252.  https://doi.org/10.1111/j.1582-4934.2008.00455.xCrossRefPubMedGoogle Scholar
  28. D’Amico L, Patane S, Grange C, Bussolati B, Isella C, Fontani L, Godio L, Cilli M, D’Amelio P, Isaia G, Medico E, Ferracini R, Roato I (2013) Primary breast cancer stem-like cells metastasise to bone, switch phenotype and acquire a bone tropism signature. Br J Cancer 108(12):2525–2536.  https://doi.org/10.1038/bjc.2013.271CrossRefPubMedPubMedCentralGoogle Scholar
  29. Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A 104(24):10158–10163.  https://doi.org/10.1073/pnas.0703478104CrossRefPubMedPubMedCentralGoogle Scholar
  30. Davis SJ, Divi V, Owen JH, Bradford CR, Carey TE, Papagerakis S, Prince MEP (2010) Metastatic potential of cancer stem cells in head and neck squamous cell carcinoma. Arch Otolaryngol 136(12):1260–1266.  https://doi.org/10.1001/archoto.2010.219CrossRefGoogle Scholar
  31. De Craene B, Berx G (2013) Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer 13(2):97–110.  https://doi.org/10.1038/nrc3447CrossRefPubMedGoogle Scholar
  32. Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5(4):275–284.  https://doi.org/10.1038/nrc1590CrossRefPubMedGoogle Scholar
  33. Dearnaley DP, Ormerod MG, Sloane JP (1991) Micrometastases in breast-cancer – long-term follow-up of the 1st patient cohort. Eur J Cancer 27(3):236–239.  https://doi.org/10.1016/0277-5379(91)90504-7CrossRefPubMedGoogle Scholar
  34. Diehn M, Clarke MF (2006) Cancer stem cells and radiotherapy: new insights into tumor radioresistance. J Natl Cancer Inst 98(24):1755–1757.  https://doi.org/10.1093/jnci/djj505CrossRefPubMedGoogle Scholar
  35. Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, Wicha MS (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17(10):1253–1270.  https://doi.org/10.1101/gad.1061803CrossRefPubMedPubMedCentralGoogle Scholar
  36. Egeblad M, Nakasone ES, Werb Z (2010) Tumors as organs: complex tissues that interface with the entire organism. Dev Cell 18(6):884–901.  https://doi.org/10.1016/j.devcel.2010.05.012CrossRefPubMedPubMedCentralGoogle Scholar
  37. Eger A, Stockinger A, Park J, Langkopf E, Mikula M, Gotzmann J, Mikulits W, Beug H, Foisner R (2004) Beta-catenin and TGF beta signalling cooperate to maintain a mesenchymal phenotype after FosER-induced epithelial to mesenchymal transition. Oncogene 23(15):2672–2680.  https://doi.org/10.1038/sj.onc.1207416CrossRefPubMedGoogle Scholar
  38. Ellis LM, Fidler IJ (1996) Angiogenesis and metastasis. Eur J Cancer 32a(14):2451–2460.  https://doi.org/10.1016/S0959-8049(96)00389-9CrossRefPubMedGoogle Scholar
  39. Eveno C, Hainaud P, Rampanou A, Bonnin P, Bakhouche S, Dupuy E, Contreres JO, Pocard M (2015) Proof of prometastatic niche induction by hepatic stellate cells. J Surg Res 194(2):496–504.  https://doi.org/10.1016/j.jss.2014.11.005CrossRefPubMedGoogle Scholar
  40. Eyler CE, Rich JN (2008) Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol 26(17):2839–2845.  https://doi.org/10.1200/Jco.2007.15.1829CrossRefPubMedPubMedCentralGoogle Scholar
  41. Fillmore CM, Kuperwasser C (2008) Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res 10(2).  https://doi.org/10.1186/bcr1982
  42. Folkins C, Shked Y, Man S, Tang T, Lee CR, Zhu ZP, Hoffman RM, Kerbel RS (2009) Glioma tumor stem-like cells promote tumor angiogenesis and vasculogenesis via vascular endothelial growth factor and stromal-derived factor 1. Cancer Res 69(18):7243–7251.  https://doi.org/10.1158/0008-5472.Can-09-0167CrossRefPubMedPubMedCentralGoogle Scholar
  43. Fulawka L, Donizy P, Halon A (2014) Cancer stem cells – the current status of an old concept: literature review and clinical approaches. Biol Res 47.  https://doi.org/10.1186/0717-6287-47-66
  44. Fuxe J, Vincent T, de Herreros AG (2010) Transcriptional crosstalk between TGF beta and stem cell pathways in tumor cell invasion role of EMT promoting Smad complexes. Cell Cycle 9(12):2363–2374.  https://doi.org/10.4161/cc.9.12.12050CrossRefPubMedGoogle Scholar
  45. Gambarotta G, Boccaccio C, Giordano S, Ando M, Stella MC, Comoglio PM (1996) Ets up-regulates MET transcription. Oncogene 13(9):1911–1917PubMedGoogle Scholar
  46. Ghosh AK, Secreto CR, Knox TR, Ding W, Mukhopadhyay D, Kay NE (2010) Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: implications for disease progression. Blood 115(9):1755–1764.  https://doi.org/10.1182/blood-2009-09-242719CrossRefPubMedPubMedCentralGoogle Scholar
  47. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1(5):555–567.  https://doi.org/10.1016/j.stem.2007.08.014CrossRefPubMedPubMedCentralGoogle Scholar
  48. Gong PJ, Hu CY, Zhou X, Wang RX, Duan Z (2017) TAT-mediated si-hWAPL inhibits the invasion and metastasis of cervical cancer stem cells. Exp Ther Med 14(6):5452–5458.  https://doi.org/10.3892/etm.2017.5229CrossRefPubMedPubMedCentralGoogle Scholar
  49. Gottschling S, Schnabel PA, Herth FJF, Herpel E (2012) Are we missing the target? – cancer stem cells and drug resistance in non-small cell lung cancer. Cancer Genom Proteom 9(5):275–286Google Scholar
  50. Grange C, Tapparo M, Collino F, Vitillo L, Damasco C, Deregibus MC, Tetta C, Bussolati B, Camussi G (2011) Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung Premetastatic niche. Cancer Res 71(15):5346–5356.  https://doi.org/10.1158/0008-5472.Can-11-0241CrossRefPubMedGoogle Scholar
  51. Greve B, Beller C, Cassens U, Sibrowski W, Gohde W (2006) The impact of erythrocyte lysing procedures on the recovery of hematopoietic progenitor cells in flow cytometric analysis. Stem Cells 24(3):793–799.  https://doi.org/10.1634/stemcells.2005-0269CrossRefPubMedGoogle Scholar
  52. Gupta PB, Onder TT, Jiang GZ, Tao K, Kuperwasser C, Weinberg RA, Lander ES (2009) Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138(4):645–659.  https://doi.org/10.1016/j.cell.2009.06.034CrossRefPubMedPubMedCentralGoogle Scholar
  53. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1(3):313–323.  https://doi.org/10.1016/j.stem.2007.06.002CrossRefPubMedGoogle Scholar
  54. Hess KR, Varadhachary GR, Taylor SH, Wei W, Raber MN, Lenzi R, Abbruzzese JL (2006) Metastatic patterns in adenocarcinoma. Cancer 106(7):1624–1633.  https://doi.org/10.1002/cncr.21778CrossRefPubMedGoogle Scholar
  55. 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 Investig 27(8):844–850.  https://doi.org/10.1080/07357900902744502CrossRefGoogle Scholar
  56. Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Mark MT, Molina H, Kohsaka S, Di Giannatale A, Ceder S, Singh S, Williams C, Soplop N, Uryu K, Pharmer L, King T, Bojmar L, Davies AE, Ararso Y, Zhang T, Zhang H, Hernandez J, Weiss JM, Dumont-Cole VD, Kramer K, Wexler LH, Narendran A, Schwartz GK, Healey JH, Sandstrom P, Labori KJ, Kure EH, Grandgenett PM, Hollingsworth MA, de Sousa M, Kaur S, Jain M, Mallya K, Batra SK, Jarnagin WR, Brady MS, Fodstad O, Muller V, Pantel K, Minn AJ, Bissell MJ, Garcia BA, Kang Y, Rajasekhar VK, Ghajar CM, Matei I, Peinado H, Bromberg J, Lyden D (2015) Tumour exosome integrins determine organotropic metastasis. Nature 527(7578):329–335.  https://doi.org/10.1038/nature15756CrossRefPubMedPubMedCentralGoogle Scholar
  57. Hu CT, Guo LL, Feng N, Zhang L, Zhou N, Ma LL, Shen L, Tong GH, Yan QW, Zhu SJ, Bian XW, Lai MD, Deng YJ, Ding YQ (2015a) MIF, secreted by human hepatic sinusoidal endothelial cells, promotes chemotaxis and outgrowth of colorectal cancer in liver prometastasis. Oncotarget 6(26):22410–22423.  https://doi.org/10.18632/oncotarget.4198CrossRefPubMedPubMedCentralGoogle Scholar
  58. Hu YB, Yan C, Mu L, Huang KY, Li XL, Tao DD, Wu YQ, Qin JC (2015b) Fibroblast-derived exosomes contribute to chemoresistance through priming cancer stem cells in colorectal cancer. PLoS One 10(5):e0125625.  https://doi.org/10.1371/journal.pone.0125625CrossRefPubMedPubMedCentralGoogle Scholar
  59. Ibrahim EE, Babaei-Jadidi R, Saadeddin A, Spencer-Dene B, Hossaini S, Abuzinadah M, Li NN, Fadhil W, Ilyas M, Bonnet D, Nateri AS (2012) Embryonic NANOG activity defines colorectal cancer stem cells and modulates through AP1-and TCF-dependent mechanisms. Stem Cells 30(10):2076–2087.  https://doi.org/10.1002/stem.1182CrossRefPubMedGoogle Scholar
  60. Ivan M, Bond JA, Prat M, Comoglio PM, Wynford Thomas D (1997) Activated ras and ret oncogenes induce over-expression of c-met (hepatocyte growth factor receptor) in human thyroid epithelial cells. Oncogene 14(20):2417–2423.  https://doi.org/10.1038/sj.onc.1201083CrossRefPubMedGoogle Scholar
  61. Ji RB, Zhang B, Zhang X, Xue JG, Yuan X, Yan YM, Wang M, Zhu W, Qian H, Xu WR (2015) Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer. Cell Cycle 14(15):2473–2483.  https://doi.org/10.1080/15384101.2015.1005530CrossRefPubMedPubMedCentralGoogle Scholar
  62. Jiang YX, Yang SW, Li PA, Luo X, Li ZY, Hao YX, Yu PW (2017) The promotion of the transformation of quiescent gastric cancer stem cells by IL-17 and the underlying mechanisms. Oncogene 36(9):1256–1264.  https://doi.org/10.1038/onc.2016.291CrossRefPubMedGoogle Scholar
  63. Jing FF, Kim HJ, Kim CH, Kim YJ, Lee JH, Kim HR (2015) Colon cancer stem cell markers CD44 and CD133 in patients with colorectal cancer and synchronous hepatic metastases. Int J Oncol 46(4):1582–1588.  https://doi.org/10.3892/ijo.2015.2844CrossRefPubMedGoogle Scholar
  64. Jordan CT (2009) Cancer stem cells: controversial or just misunderstood? Cell Stem Cell 4(3):203–205.  https://doi.org/10.1016/j.stem.2009.02.003CrossRefPubMedPubMedCentralGoogle Scholar
  65. Junttila MR, de Sauvage FJ (2013) Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 501(7467):346–354.  https://doi.org/10.1038/nature12626CrossRefPubMedGoogle Scholar
  66. Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, Zhu ZP, Hicklin D, Wu Y, Port JL, Altorki N, Port ER, Ruggero D, Shmelkov SV, Jensen KK, Rafii S, Lyden D (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438(7069):820–827.  https://doi.org/10.1038/nature04186CrossRefPubMedPubMedCentralGoogle Scholar
  67. 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.  https://doi.org/10.1186/bcr3099CrossRefPubMedPubMedCentralGoogle Scholar
  68. Kentrou NA, Tsagarakis NJ, Tzanetou K, Damala M, Papadimitriou KA, Skoumi D, Stratigaki A, Anagnostopoulos NI, Malamou-Lada E, Athanassiadou P, Paterakis G (2011) An improved flow cytometric assay for detection and discrimination between malignant cells and atypical mesothelial cells, in serous cavity effusions. Cytomtry B Clin Cytom 80b(5):324–334.  https://doi.org/10.1002/cyto.b.20608CrossRefGoogle Scholar
  69. Kienast Y, von Baumgarten L, Fuhrmann M, Klinkert WEF, Goldbrunner R, Herms J, Winkler F (2010) Real-time imaging reveals the single steps of brain metastasis formation. Nat Med 16(1):116–U157.  https://doi.org/10.1038/nm.2072CrossRefPubMedGoogle Scholar
  70. Klein A, Schwartz H, Sagi-Assif O, Meshel T, Izraely S, Ben Menachem S, Bengaiev R, Ben-Shmuel A, Nahmias C, Couraud PO, Witz IP, Erez N (2015) Astrocytes facilitate melanoma brain metastasis via secretion of IL-23. J Pathol 236(1):116–127.  https://doi.org/10.1002/path.4509CrossRefPubMedGoogle Scholar
  71. Korkaya H, Paulson A, Iovino F, Wicha MS (2008) HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene 27(47):6120–6130.  https://doi.org/10.1038/onc.2008.207CrossRefPubMedPubMedCentralGoogle Scholar
  72. Krivtsov AV, Twomey D, Feng ZH, Stubbs MC, Wang YZ, Faber J, Levine JE, Wang J, Hahn WC, Gilliland DG, Golub TR, Armstrong SA (2006) Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 442(7104):818–822.  https://doi.org/10.1038/nature04980CrossRefPubMedGoogle Scholar
  73. Kucia M, Reca R, Miekus K, Wanzeck J, Wojakowski W, Janowska-Wieczorek A, Ratajczak J, Ratajczak MZ (2005) Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells 23(7):879–894.  https://doi.org/10.1634/stemcells.2004-0342CrossRefPubMedGoogle Scholar
  74. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67(3):1030–1037.  https://doi.org/10.1158/0008-5472.CAN-06-2030CrossRefPubMedGoogle Scholar
  75. Li XX, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, Hilsenbeck SG, Pavlick A, Zhang XM, Chamness GC, Wong H, Rosen J, Chang JC (2008) Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst 100(9):672–679.  https://doi.org/10.1093/jnci/djn123CrossRefPubMedGoogle Scholar
  76. Li CMC, Gocheva V, Oudin MJ, Bhutkar A, Wang SY, Date SR, Ng SR, Whittaker CA, Bronson RT, Snyder EL, Gertler FB, Jacks T (2015) Foxa2 and Cdx2 cooperate with Nkx2-1 to inhibit lung adenocarcinoma metastasis. Genes Dev 29(17):1850–1862.  https://doi.org/10.1101/gad.267393.115CrossRefPubMedPubMedCentralGoogle Scholar
  77. Lianidou ES, Markou A (2011) Circulating tumor cells in breast cancer: detection systems, molecular characterization, and future challenges. Clin Chem 57(9):1242–1255.  https://doi.org/10.1373/clinchem.2011.165068CrossRefPubMedGoogle Scholar
  78. Liu HP, Patel MR, Prescher JA, Patsialou A, Qian DL, Lin JH, Wen S, Chang YF, Bachmann MH, Shimono Y, Dalerba P, Adorno M, Lobo N, Bueno J, Dirbas FM, Goswami S, Somlo G, Condeelis J, Contag CH, Gambhir SS, Clarke MF (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.  https://doi.org/10.1073/pnas.1006732107CrossRefPubMedPubMedCentralGoogle Scholar
  79. Lloyd MC, Cunningham JJ, Bui MM, Gillies RJ, Brown JS, Gatenby RA (2016) Darwinian dynamics of intratumoral heterogeneity: not solely random mutations but also variable environmental selection forces. Cancer Res 76(11):3136–3144.  https://doi.org/10.1158/0008-5472.Can-15-2962CrossRefPubMedPubMedCentralGoogle Scholar
  80. Lorenzato A, Olivero M, Patane S, Rosso E, Oliaro A, Comoglio PM, Di Renzo MF (2002) Novel somatic mutations of the MET oncogene in human carcinoma metastases activating cell motility and invasion. Cancer Res 62(23):7025–7030PubMedGoogle Scholar
  81. Lotti F, Jarrar AM, Pai RK, Hitomi M, Lathia J, Mace A, Gantt GA, Sukhdeo K, DeVecchio J, Vasanji A, Leahy P, Hjelmeland AB, Kalady MF, Rich JN (2013) Chemotherapy activates cancer-associated fibroblasts to maintain colorectal cancer-initiating cells by IL-17A. J Exp Med 210(13):2851–2872.  https://doi.org/10.1084/jem.20131195CrossRefPubMedPubMedCentralGoogle Scholar
  82. Luzzi KJ, MacDonald IC, Schmidt EE, Kerkvliet N, Morris VL, Chambers AF, Groom AC (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.  https://doi.org/10.1016/S0002-9440(10)65628-3CrossRefPubMedPubMedCentralGoogle Scholar
  83. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704–715.  https://doi.org/10.1016/j.cell.2008.03.027CrossRefPubMedPubMedCentralGoogle Scholar
  84. Marchio S, Soster M, Cardaci S, Muratore A, Bartolini A, Barone V, Ribero D, Monti M, Bovino P, Sun J, Giavazzi R, Asioli S, Cassoni P, Capussotti L, Pucci P, Bugatti A, Rusnati M, Pasqualini R, Arap W, Bussolino F (2012) A complex of alpha(6) integrin and E-cadherin drives liver metastasis of colorectal cancer cells through hepatic angiopoietin-like 6. EMBO Mol Med 4(11):1156–1175.  https://doi.org/10.1002/emmm.201101164CrossRefPubMedPubMedCentralGoogle Scholar
  85. McGowan PM, Simedrea C, Ribot EJ, Foster PJ, Palmieri D, Steeg PS, Allan AL, Chambers AF (2011) Notch1 inhibition alters the CD44(hi)/CD24(lo) population and reduces the formation of brain metastases from breast cancer. Mol Cancer Res 9(7):834–844.  https://doi.org/10.1158/1541-7786.Mcr-10-0457CrossRefPubMedPubMedCentralGoogle Scholar
  86. Melo SA, Sugimoto H, O’Connell JT, Kato N, Villanueva A, Vidal A, Qiu L, Vitkin E, Perelman LT, Melo CA, Lucci A, Ivan C, Calin GA, Kalluri R (2014) Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell 26(5):707–721.  https://doi.org/10.1016/j.ccell.2014.09.005CrossRefPubMedPubMedCentralGoogle Scholar
  87. Milane L, Singh A, Mattheolabakis G, Suresh M, Amiji MM (2015) Exosome mediated communication within the tumor microenvironment. J Control Release 219:278–294.  https://doi.org/10.1016/j.jconrel.2015.06.029CrossRefPubMedGoogle Scholar
  88. Morales M, Arenas EJ, Urosevic J, Guiu M, Fernandez E, Planet E, Fenwick RB, Fernandez-Ruiz S, Salvatella X, Reverter D, Carracedo A, Massague J, Gomis RR (2014) RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation. EMBO Mol Med 6(7):865–881.  https://doi.org/10.15252/emmm.201303675CrossRefPubMedPubMedCentralGoogle Scholar
  89. Mueller MM, Fusenig NE (2004) Friends or foes – bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 4(11):839–849.  https://doi.org/10.1038/nrc1477CrossRefPubMedGoogle Scholar
  90. Nielsen SR, Quaranta V, Linford A, Emeagi P, Rainer C, Santos A, Ireland L, Sakai T, Sakai K, Kim YS, Engle D, Campbell F, Palmer D, Ko JH, Tuveson DA, Hirsch E, Mielgo A, Schmid MC (2016) Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis (vol 18, pg 549, 2016). Nat Cell Biol 18(7):822–822.  https://doi.org/10.1038/ncb3377CrossRefPubMedGoogle Scholar
  91. Nolte SM, Venugopal C, McFarlane N, Morozova O, Hallett RM, O’Farrell E, Manoranjan B, Murty NK, Klurfan P, Kachur E, Provias JP, Farrokhyar F, Hassell JA, Marra M, Singh SK (2013) A cancer stem cell model for studying brain metastases from primary lung cancer. JNCI, J Natl Cancer Inst 105(8):551–562.  https://doi.org/10.1093/jnci/djt022CrossRefPubMedGoogle Scholar
  92. Nowell PC (1988) Citation classic – the clonal evolution of tumor-cell populations. Cc/Life Sci 18:19–19Google Scholar
  93. O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445(7123):106–110.  https://doi.org/10.1038/nature05372CrossRefPubMedGoogle Scholar
  94. Obenauf AC, Massague J (2015) Surviving at a distance: organ-specific metastasis. Trends Cancer 1(1):76–91.  https://doi.org/10.1016/j.trecan.2015.07.009CrossRefPubMedPubMedCentralGoogle Scholar
  95. Okuda H, Xing F, Pandey PR, Sharma S, Watabe M, Pai SK, Mo YY, Iiizumi-Gairani M, Hirota S, Liu Y, Wu KR, Pochampally R, Watabe K (2013) miR-7 suppresses brain metastasis of breast cancer stem-like cells by modulating KLF4. Cancer Res 73(4):1434–1444.  https://doi.org/10.1158/0008-5472.Can-12-2037CrossRefPubMedPubMedCentralGoogle Scholar
  96. Ono M, Kosaka N, Tominaga N, Yoshioka Y, Takeshita F, Takahashi RU, Yoshida M, Tsuda H, Tamura K, Ochiya T (2014) Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells. Sci Signal 7(332):ra63.  https://doi.org/10.1126/scisignal.2005231CrossRefPubMedGoogle Scholar
  97. Pang R, Law WL, Chu ACY, Poon JT, Lam CSC, Chow AKM, Ng L, Cheung LWH, Lan XR, Lan HY, Tan VPY, Yau TC, Poon RT, Wong BCY (2010) A subpopulation of CD26(+) cancer stem cells with metastatic capacity in human colorectal cancer. Cell Stem Cell 6(6):603–615.  https://doi.org/10.1016/j.stem.2010.04.001CrossRefPubMedGoogle Scholar
  98. Pardal R, Clarke MF, Morrison SJ (2003) Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 3(12):895–902.  https://doi.org/10.1038/nrc1232CrossRefPubMedGoogle Scholar
  99. Pattabiraman DR, Weinberg RA (2014) Tackling the cancer stem cells – what challenges do they pose? Nat Rev Drug Discov 13(7):497–512.  https://doi.org/10.1038/nrd4253CrossRefPubMedPubMedCentralGoogle Scholar
  100. Plaks V, Kong NW, Werb Z (2015) The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell 16(3):225–238.  https://doi.org/10.1016/j.stem.2015.02.015CrossRefPubMedPubMedCentralGoogle Scholar
  101. Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE (2007) Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A 104(3):973–978.  https://doi.org/10.1073/pnas.0610117104CrossRefPubMedPubMedCentralGoogle Scholar
  102. Ren F, Sheng WQ, Du X (2013) CD133: a cancer stem cells marker, is used in colorectal cancers. World J Gastroenterol 19(17):2603–2611.  https://doi.org/10.3748/wjg.v19.i17.2603CrossRefPubMedPubMedCentralGoogle Scholar
  103. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414(6859):105–111.  https://doi.org/10.1038/35102167CrossRefPubMedGoogle Scholar
  104. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445(7123):111–115.  https://doi.org/10.1038/nature05384CrossRefPubMedGoogle Scholar
  105. Roccaro AM, Sacco A, Maiso P, Azab AK, Tai YT, Reagan M, Azab F, Flores LM, Campigotto F, Weller E, Anderson KC, Scadden DT, Ghobrial IM (2013) BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression (vol 123, pg 1542, 2013). J Clin Invest 123(8):3635–3635.  https://doi.org/10.1172/Jci71663CrossRefPubMedCentralGoogle Scholar
  106. Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH (2008) Identification of cells initiating human melanomas. Nature 451(7176):345–349.  https://doi.org/10.1038/nature06489CrossRefPubMedPubMedCentralGoogle Scholar
  107. Scheel C, Eaton EN, Li SHJ, Chaffer CL, Reinhardt F, Kah KJ, Bell G, Guo W, Rubin J, Richardson AL, Weinberg RA (2011) Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell 145(6):926–940.  https://doi.org/10.1016/j.cell.2011.04.029CrossRefPubMedPubMedCentralGoogle Scholar
  108. Seow Y, Wood MJ (2009) Biological gene delivery vehicles: beyond viral vectors. Mol Ther 17(5):767–777.  https://doi.org/10.1038/mt.2009.41CrossRefPubMedPubMedCentralGoogle Scholar
  109. Shin SY, Rath O, Zebisch A, Choo SM, Kolch W, Cho KH (2010) Functional roles of multiple feedback loops in extracellular signal-regulated kinase and Wnt signaling pathways that regulate epithelial-mesenchymal transition. Cancer Res 70(17):6715–6724.  https://doi.org/10.1158/0008-5472.Can-10-1377CrossRefPubMedPubMedCentralGoogle Scholar
  110. Shmelkov SV, Butler JM, Hooper AT, Hormigo A, Kushner J, Milde T, St Clair R, Baljevic M, White I, Jin DK, Chadburn A, Murphy AJ, Valenzuela DM, Gale NW, Thurston G, Yancopoulos GD, D’Angelica M, Kemeny N, Lyden D, Rafii S (2008) CD133 expression is not restricted to stem cells, and both CD133(+) and CD133(−) metastatic colon cancer cells initiate tumors. J Clin Invest 118(6):2111–2120.  https://doi.org/10.1172/Jci34401CrossRefPubMedPubMedCentralGoogle Scholar
  111. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63(18):5821–5828PubMedGoogle Scholar
  112. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401.  https://doi.org/10.1038/nature03128CrossRefPubMedGoogle Scholar
  113. Sottnik JL, Dai JL, Zhang HL, Campbell B, Keller ET (2015) Tumor-induced pressure in the bone microenvironment causes osteocytes to promote the growth of prostate cancer bone metastases. Cancer Res 75(11):2151–2158.  https://doi.org/10.1158/0008-5472.Can-14-2493CrossRefPubMedPubMedCentralGoogle Scholar
  114. Sun YF, Yang XR, Zhou J, Qiu SJ, Fan J, Xu Y (2011) Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance. J Cancer Res Clin 137(8):1151–1173.  https://doi.org/10.1007/s00432-011-0988-yCrossRefGoogle Scholar
  115. Suva ML, Riggi N, Stehle JC, Baumer K, Tercier S, Joseph JM, Suva D, Clement V, Provero P, Cironi L, Osterheld MC, Guillou L, Stamenkovic I (2009) Identification of cancer stem cells in Ewing’s sarcoma. Cancer Res 69(5):1776–1781.  https://doi.org/10.1158/0008-5472.Can-08-2242CrossRefPubMedGoogle Scholar
  116. Takayama H, Larochelle WJ, Anver M, Bockman DE, Merlino G (1996) Scatter factor/hepatocyte growth factor as a regulator of skeletal muscle and neural crest development. Proc Natl Acad Sci U S A 93(12):5866–5871.  https://doi.org/10.1073/pnas.93.12.5866CrossRefPubMedPubMedCentralGoogle Scholar
  117. Taylor DD, Gercel-Taylor C (2008) MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 110(1):13–21.  https://doi.org/10.1016/j.ygyno.2008.04.033CrossRefPubMedGoogle Scholar
  118. Tayyeb B, Parvin M (2016) Pathogenesis of breast cancer metastasis to brain: a comprehensive approach to the signaling network. Mol Neurobiol 53(1):446–454.  https://doi.org/10.1007/s12035-014-9023-zCrossRefPubMedGoogle Scholar
  119. Thomas D, Thiagarajan PS, Rai V, Reizes O, Lathia J, Egelhoff T (2016) Increased cancer stem cell invasion is mediated by myosin IIB and nuclear translocation. Oncotarget 7(30):47586–47592.  https://doi.org/10.18632/oncotarget.9896CrossRefPubMedPubMedCentralGoogle Scholar
  120. Timmerman LA, Grego-Bessa J, Raya A, Bertran E, Perez-Pomares JM, Diez J, Aranda S, Palomo S, McCormick F, Izpisua-Belmonte JC, de la Pompa JL (2004) Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev 18(1):99–115.  https://doi.org/10.1101/gad.276304CrossRefPubMedPubMedCentralGoogle Scholar
  121. Tu SM, Lin SH, Logothetis CJ (2002) Stem-cell origin of metastasis and heterogeneity in solid tumours. Lancet Oncol 3(8):508–513.  https://doi.org/10.1016/S1470-2045(02)00820-3CrossRefPubMedGoogle Scholar
  122. Valcourt U, Kowanetz M, Niimi H, Heldin CH, Moustakas A (2005) TGF-ss and the smad signaling pathway suppor transcriptomic reprogramming during epithelial-mesenchymal cell transition. Mol Biol Cell 16(4):1987–2002.  https://doi.org/10.1091/mbc.E04-08-0658CrossRefPubMedPubMedCentralGoogle Scholar
  123. Vermeulen L, Melo FDSE, van der Heijden M, Cameron K, de Jong JH, Borovski T, Tuynman JB, Todaro M, Merz C, Rodermond H, Sprick MR, Kemper K, Richel DJ, Stassi G, Medema JP (2010) Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol 12(5):468–U121.  https://doi.org/10.1038/ncb2048CrossRefPubMedGoogle Scholar
  124. Wang M, Zhao C, Shi H, Zhang B, Zhang L, Zhang X, Wang S, Wu X, Yang T, Huang F, Cai J, Zhu Q, Zhu W, Qian H, Xu W (2014) Deregulated microRNAs in gastric cancer tissue-derived mesenchymal stem cells: novel biomarkers and a mechanism for gastric cancer. Br J Cancer 110(5):1199–1210.  https://doi.org/10.1038/bjc.2014.14CrossRefPubMedPubMedCentralGoogle Scholar
  125. Wang H, Yu CJ, Gao X, Welte T, Muscarella AM, Tian L, Zhao H, Zhao Z, Du SY, Tao JN, Lee B, Westbrook TF, Wong STC, Jin X, Rosen JM, Osborne CK, Zhang XHF (2015) The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells. Cancer Cell 27(2):193–210.  https://doi.org/10.1016/j.ccell.2014.11.017CrossRefPubMedPubMedCentralGoogle Scholar
  126. Winslow MM, Dayton TL, Verhaak RGW, Kim-Kiselak C, Snyder EL, Feldser DM, Hubbard DD, DuPage MJ, Whittaker CA, Hoersch S, Yoon S, Crowley D, Bronson RT, Chiang DY, Meyerson M, Jacks T (2011) Suppression of lung adenocarcinoma progression by Nkx2-1. Nature 473(7345):101–120.  https://doi.org/10.1038/nature09881CrossRefPubMedPubMedCentralGoogle Scholar
  127. Wirtz D, Konstantopoulos K, Searson PC (2011) The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat Rev Cancer 11(7):512–522.  https://doi.org/10.1038/nrc3080CrossRefPubMedPubMedCentralGoogle Scholar
  128. Woodward WA, Chen MS, Behbod F, Alfaro MP, Buchholz TA, Rosen JM (2007) WNT/beta-catenin mediates radiation resistance of mouse mammary progenitor cells (vol 104, pg 618, 2007). Proc Natl Acad Sci U S A 104(17):7307–7307.  https://doi.org/10.1073/pnas.0702664104CrossRefGoogle Scholar
  129. Xu F, Dai CL, Zhang R, Zhao Y, Peng SL, Jia CJ (2012) Nanog: a potential biomarker for liver metastasis of colorectal cancer. Dig Dis Sci 57(9):2340–2346.  https://doi.org/10.1007/s10620-012-2182-8CrossRefPubMedGoogle Scholar
  130. Zeuner A, Todaro M, Stassi G, De Maria R (2014) Colorectal cancer stem cells: from the crypt to the clinic. Cell Stem Cell 15(6):692–705.  https://doi.org/10.1016/j.stem.2014.11.012CrossRefPubMedGoogle Scholar
  131. Zhang M, Behbod F, Atkinson RL, Landis MD, Kittrell F, Edwards D, Medina D, Tsimelzon A, Hilsenbeck S, Green JE, Michalowska AM, Rosen JM (2008a) Identification of tumor-initiating cells in a p53-null mouse model of breast cancer. Cancer Res 68(12):4674–4682.  https://doi.org/10.1158/0008-5472.CAN-07-6353CrossRefPubMedPubMedCentralGoogle Scholar
  132. Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang TH, Nephew KP (2008b) Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 68(11):4311–4320.  https://doi.org/10.1158/0008-5472.CAN-08-0364CrossRefPubMedPubMedCentralGoogle Scholar
  133. Zhang XHF, Wang QQ, Gerald W, Hudis CA, Norton L, Smid M, Foekens JA, Massague J (2009) Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell 16(1):67–78.  https://doi.org/10.1016/j.ccr.2009.05.017CrossRefPubMedPubMedCentralGoogle Scholar
  134. Zhang SS, Han ZP, Jing YY, Tao SF, Li TJ, Wang H, Wang Y, Li R, Yang Y, Zhao X, Xu XD, Yu ED, Rui YC, Liu HJ, Zhang L, Wei LX (2012) CD133(+)CXCR4(+) colon cancer cells exhibit metastatic potential and predict poor prognosis of patients. BMC Med 10.  https://doi.org/10.1186/1741-7015-10-85
  135. Zhang XHF, Jin X, Malladi S, Zou YL, Wen YH, Brogi E, Smid M, Foekens JA, Massague J (2013) Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma. Cell 154(5):1060–1073.  https://doi.org/10.1016/j.cell.2013.07.036CrossRefPubMedPubMedCentralGoogle Scholar
  136. Zhang L, Zhan SY, Yao J, Lowery FJ, Zhang QL, Huang WC, Li P, Li M, Wang X, Zhang CY, Wang H, Ellis K, Cheerathodi M, McCarty JH, Palmieri D, Saunus J, Lakhani S, Huang SY, Sahin AA, Aldape KD, Steeg PS, Yu DH (2015) Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature 527(7576):100–104.  https://doi.org/10.1038/nature15376CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Genetics and Bioengineering, Faculty of EngineeringYeditepe UniversityIstanbulTurkey

Personalised recommendations