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Understanding Cancer Invasion and Metastasis

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Cancer Bioinformatics

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Abstract

Cancer is a deadly disease in large part because, if not stopped, will generally evolve to the metastatic stage, i.e., cancer cells spread from the primary site to new locations (generally different organs) through blood circulation or the lymphatic system. For largely unknown reasons, metastatic cancers tend to exhibit distinct growth patterns from its primary cancer counterpart, growing substantially faster and metastasizing more easily. Recent statistics show that metastatic cancer is responsible for approximately 90 % of all cancer-related mortalities. While it is known to be the deadliest stage of a cancer, the current understanding of the biology of metastatic cancer is rather limited. Some of the very basic questions such as: what drives a primary cancer to metastasize; why some cancers tend to metastasize more easily than the other cancers, e.g., melanoma versus basal cell carcinoma; and why metastatic cancers tend to grow much faster than the corresponding primary cancer, still have no clear answers. This may be the result of: (1) the true challenging nature of these questions, and (2) the lack of adequate investment and hence efforts into metastatic cancer research. This unfortunate reality is probably due to the general belief in the field that little can be done once a cancer has metastasized.

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References

  • Aguirre-Ghiso JA (2007) Models, mechanisms and clinical evidence for cancer dormancy. Nature reviews Cancer 7: 834-846

    Article  Google Scholar 

  • Alberts B, Johnson A, Lewis J et al. (2002) The extracellular matrix of animals.

    Google Scholar 

  • Alexander NR, Branch KM, Parekh A et al. (2008) Extracellular matrix rigidity promotes invadopodia activity. Curr Biol 18: 1295-1299

    Article  Google Scholar 

  • Alix-Panabieres C, Riethdorf S, Pantel K (2008) Circulating tumor cells and bone marrow micrometastasis. Clinical cancer research: an official journal of the American Association for Cancer Research 14: 5013-5021

    Article  Google Scholar 

  • Amirkhosravi A, Mousa SA, Amaya M et al. (2003) Inhibition of tumor cell-induced platelet aggregation and lung metastasis by the oral GpIIb/IIIa antagonist XV454. Thromb Haemost 90: 549-554

    Google Scholar 

  • Artym VV, Zhang Y, Seillier-Moiseiwitsch F et al. (2006) Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: defining the stages of invadopodia formation and function. Cancer research 66: 3034-3043

    Article  Google Scholar 

  • Barcellos-Hoff M, Dix TA (1996) Redox-mediated activation of latent transforming growth factor-beta 1. Molecular endocrinology (Baltimore, Md) 10: 1077-1083

    Google Scholar 

  • Barkan D, Green JE, Chambers AF (2010) Extracellular matrix: a gatekeeper in the transition from dormancy to metastatic growth. European journal of cancer 46: 1181-1188

    Article  Google Scholar 

  • Barkan D, Kleinman H, Simmons JL et al. (2008) Inhibition of metastatic outgrowth from single dormant tumor cells by targeting the cytoskeleton. Cancer research 68: 6241-6250

    Article  Google Scholar 

  • Bendas G, Borsig L (2012) Cancer cell adhesion and metastasis: selectins, integrins, and the inhibitory potential of heparins. Int J Cell Biol 2012: 676731

    Article  Google Scholar 

  • Bharadwaj AG, Kovar JL, Loughman E et al. (2009) Spontaneous metastasis of prostate cancer is promoted by excess hyaluronan synthesis and processing. Am J Pathol 174: 1027-1036

    Article  Google Scholar 

  • Chen H, Paradies NE, Fedor-Chaiken M et al. (1997) E-cadherin mediates adhesion and suppresses cell motility via distinct mechanisms. Journal of cell science 110 (Pt 3): 345-356

    Google Scholar 

  • Cho EH, Wendel M, Luttgen M et al. (2012a) Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors. Phys Biol 9: 016001

    Article  Google Scholar 

  • Cho JA, Park H, Lim EH et al. (2012b) Exosomes from breast cancer cells can convert adipose tissue-derived mesenchymal stem cells into myofibroblast-like cells. Int J Oncol 40: 130-138

    Google Scholar 

  • Chung C, Beecham M, Mauck RL et al. (2009) The influence of degradation characteristics of hyaluronic acid hydrogels on in vitro neocartilage formation by mesenchymal stem cells. Biomaterials 30: 4287-4296

    Article  Google Scholar 

  • Craig EA, Parker P, Camenisch TD (2009) Size-dependent regulation of Snail2 by hyaluronan: its role in cellular invasion. Glycobiology 19: 890-898

    Article  Google Scholar 

  • Dallas MR, Liu G, Chen WC et al. (2012) Divergent roles of CD44 and carcinoembryonic antigen in colon cancer metastasis. FASEB journal: official publication of the Federation of American Societies for Experimental Biology 26: 2648-2656

    Article  Google Scholar 

  • Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425: 577-584

    Article  Google Scholar 

  • Dimitroff CJ, Descheny L, Trujillo N et al. (2005) Identification of leukocyte E-selectin ligands, P-selectin glycoprotein ligand-1 and E-selectin ligand-1, on human metastatic prostate tumor cells. Cancer research 65: 5750-5760

    Article  Google Scholar 

  • Douma S, Van Laar T, Zevenhoven J et al. (2004) Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature 430: 1034-1039

    Article  Google Scholar 

  • Eccles SA, Welch DR (2007) Metastasis: recent discoveries and novel treatment strategies. Lancet 369: 1742-1757

    Article  Google Scholar 

  • Fidler IJ (2003) The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nature reviews Cancer 3: 453-458

    Article  Google Scholar 

  • Fidler IJ, Poste G (2008) The “seed and soil” hypothesis revisited. Lancet Oncol 9: 808

    Article  Google Scholar 

  • Garofalo A, Chirivi RG, Foglieni C et al. (1995) Involvement of the very late antigen 4 integrin on melanoma in interleukin 1-augmented experimental metastases. Cancer research 55: 414-419

    Google Scholar 

  • Gasic GJ (1984) Role of plasma, platelets, and endothelial cells in tumor metastasis. Cancer metastasis reviews 3: 99-114

    Article  Google Scholar 

  • Gasic GJ, Gasic TB, Stewart CC (1968) Antimetastatic effects associated with platelet reduction. Proc Natl Acad Sci U S A 61: 46-52

    Article  Google Scholar 

  • Gay LJ, Felding-Habermann B (2011) Contribution of platelets to tumour metastasis. Nature reviews Cancer 11: 123-134

    Article  Google Scholar 

  • Gui T, Sun Y, Shimokado A et al. (2012) The Roles of Mitogen-Activated Protein Kinase Pathways in TGF-beta-Induced Epithelial-Mesenchymal Transition. J Signal Transduct 2012: 289243

    Google Scholar 

  • Gupta GP, Massague J (2006) Cancer metastasis: building a framework. Cell 127: 679-695

    Article  Google Scholar 

  • Gupta SC, Hevia D, Patchva S et al. (2012) Upsides and downsides of reactive oxygen species for cancer: the roles of reactive oxygen species in tumorigenesis, prevention, and therapy. Antioxid Redox Signal 16: 1295-1322

    Article  Google Scholar 

  • Hagedorn EJ, Sherwood DR (2011) Cell invasion through basement membrane: the anchor cell breaches the barrier. Current Opinion in Cell Biology 23: 589-596

    Article  Google Scholar 

  • Hagedorn EJ, Ziel JW, Morrissey MA et al. (2013) The netrin receptor DCC focuses invadopodia-driven basement membrane transmigration in vivo. The Journal of cell biology 201: 903-913

    Article  Google Scholar 

  • Hammes HP, Lin J, Wagner P et al. (2004) Angiopoietin-2 causes pericyte dropout in the normal retina: evidence for involvement in diabetic retinopathy. Diabetes 53: 1104-1110

    Article  Google Scholar 

  • Hansen LK, Albrecht JH (1999) Regulation of the hepatocyte cell cycle by type I collagen matrix: role of cyclin D1. Journal of cell science 112 (Pt 17): 2971-2981

    Google Scholar 

  • Hay ED (1981) Extracellular matrix. The Journal of cell biology 91: 205s-223s

    Article  Google Scholar 

  • Hill A, McFarlane S, Mulligan K et al. (2006) Cortactin underpins CD44-promoted invasion and adhesion of breast cancer cells to bone marrow endothelial cells. Oncogene 25: 6079-6091

    Article  Google Scholar 

  • Hiraga T, Ito S, Nakamura H (2013) Cancer stem-like cell marker CD44 promotes bone metastases by enhancing tumorigenicity, cell motility, and hyaluronan production. Cancer research 73: 4112-4122

    Article  Google Scholar 

  • Hofbauer R, Frass M, Salfinger H et al. (1999) Propofol reduces the migration of human leukocytes through endothelial cell monolayers. Crit Care Med 27: 1843-1847

    Article  Google Scholar 

  • Horak CE, Lee JH, Marshall JC et al. (2008) The role of metastasis suppressor genes in metastatic dormancy. APMIS 116: 586-601

    Article  Google Scholar 

  • Hsu C, Morohashi Y, Yoshimura S et al. (2010) Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C. The Journal of cell biology 189: 223-232

    Article  Google Scholar 

  • Ina K, Kitamura H, Tatsukawa S et al. (2011) Significance of alpha-SMA in myofibroblasts emerging in renal tubulointerstitial fibrosis. Histology and histopathology 26: 855-866

    Google Scholar 

  • Jain M, Rivera S, Monclus EA et al. (2013) Mitochondrial Reactive Oxygen Species Regulate Transforming Growth Factor-β Signaling. Journal of Biological Chemistry 288: 770-777

    Article  Google Scholar 

  • Kahlert C, Kalluri R (2013) Exosomes in tumor microenvironment influence cancer progression and metastasis. J Mol Med (Berl) 91: 431-437

    Article  Google Scholar 

  • Kim YN, Koo KH, Sung JY et al. (2012) Anoikis resistance: an essential prerequisite for tumor metastasis. Int J Cell Biol 2012: 306879

    Article  Google Scholar 

  • Kothapalli CR, Ramamurthi A (2009) Biomimetic regeneration of elastin matrices using hyaluronan and copper ion cues. Tissue engineering Part A 15: 103-113

    Article  Google Scholar 

  • Kothapalli CR, Taylor PM, Smolenski RT et al. (2009) Transforming growth factor beta 1 and hyaluronan oligomers synergistically enhance elastin matrix regeneration by vascular smooth muscle cells. Tissue engineering Part A 15: 501-511

    Article  Google Scholar 

  • Langley RR, Fidler IJ (2011) The seed and soil hypothesis revisited–the role of tumor-stroma interactions in metastasis to different organs. Int J Cancer 128: 2527-2535

    Article  Google Scholar 

  • Lee JM, Dedhar S, Kalluri R et al. (2006) The epithelial–mesenchymal transition: new insights in signaling, development, and disease. The Journal of cell biology 172: 973-981

    Article  Google Scholar 

  • Li J, Zhao Z, Wang J et al. (2008) The role of extracellular matrix, integrins, and cytoskeleton in mechanotransduction of centrifugal loading. Mol Cell Biochem 309: 41-48

    Article  Google Scholar 

  • Lindqvist U (1997) Is serum hyaluronan a helpful tool in the management of patients with liver diseases? J Intern Med 242: 67-71

    Article  Google Scholar 

  • Liu RM, Gaston Pravia KA (2010) Oxidative stress and glutathione in TGF-beta-mediated fibrogenesis. Free Radic Biol Med 48: 1-15

    Article  Google Scholar 

  • Lu X, Mu E, Wei Y et al. (2011) VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging alpha4beta1-positive osteoclast progenitors. Cancer Cell 20: 701-714

    Article  Google Scholar 

  • Lyons RM, Keski-Oja J, Moses HL (1988) Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium. The Journal of cell biology 106: 1659-1665

    Article  Google Scholar 

  • Martinez-Outschoorn UE, Pavlides S, Howell A et al. (2011) Stromal-epithelial metabolic coupling in cancer: integrating autophagy and metabolism in the tumor microenvironment. The international journal of biochemistry & cell biology 43: 1045-1051

    Article  Google Scholar 

  • Meadows GG (2005) Integration/Interaction of Oncologic Growth. Springer-Verlag Inc., New York

    Book  Google Scholar 

  • Meng S, Tripathy D, Frenkel EP et al. (2004) Circulating tumor cells in patients with breast cancer dormancy. Clinical cancer research: an official journal of the American Association for Cancer Research 10: 8152-8162

    Article  Google Scholar 

  • Migneco G, Whitaker-Menezes D, Chiavarina B et al. (2010) Glycolytic cancer associated fibroblasts promote breast cancer tumor growth, without a measurable increase in angiogenesis: evidence for stromal-epithelial metabolic coupling. Cell Cycle 9: 2412-2422

    Article  Google Scholar 

  • Misra S, Heldin P, Hascall VC et al. (2011) Hyaluronan-CD44 interactions as potential targets for cancer therapy. FEBS J 278: 1429-1443

    Article  Google Scholar 

  • Miyazawa K, Shinozaki M, Hara T et al. (2002) Two major Smad pathways in TGF-beta superfamily signalling. Genes Cells 7: 1191-1204

    Article  Google Scholar 

  • Molloy TJ, Roepman P, Naume B et al. (2012) A prognostic gene expression profile that predicts circulating tumor cell presence in breast cancer patients. PloS one 7: e32426

    Article  Google Scholar 

  • Montgomery N, Hill A, McFarlane S et al. (2012) CD44 enhances invasion of basal-like breast cancer cells by upregulating serine protease and collagen-degrading enzymatic expression and activity. Breast Cancer Res 14: R84

    Article  Google Scholar 

  • Montserrat N, Gallardo A, Escuin D et al. (2011) Repression of E-cadherin by SNAIL, ZEB1, and TWIST in invasive ductal carcinomas of the breast: a cooperative effort? Human pathology 42: 103-110

    Article  Google Scholar 

  • Nash KT, Welch DR, Nash K et al. (2006) The KISS1 metastasis suppressor: mechanistic insights and clinical utility. Frontiers in bioscience: a journal and virtual library 11: 647

    Article  Google Scholar 

  • Nataatmadja M, West J, West M (2006) Overexpression of transforming growth factor-beta is associated with increased hyaluronan content and impairment of repair in Marfan syndrome aortic aneurysm. Circulation 114: I371-377

    Article  Google Scholar 

  • Okahara H, Yagita H, Miyake K et al. (1994) Involvement of very late activation antigen 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) in tumor necrosis factor alpha enhancement of experimental metastasis. Cancer research 54: 3233-3236

    Google Scholar 

  • Ostrowski M, Carmo NB, Krumeich S et al. (2010) Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 12: 19-30; sup pp 11-13

    Google Scholar 

  • Owen SC, Shoichet MS (2010) Design of three-dimensional biomimetic scaffolds. Journal of Biomedical Materials Research Part A 94A: 1321-1331

    Google Scholar 

  • Paez D, Labonte MJ, Bohanes P et al. (2012) Cancer dormancy: a model of early dissemination and late cancer recurrence. Clinical cancer research: an official journal of the American Association for Cancer Research 18: 645-653

    Article  Google Scholar 

  • Palumbo JS, Talmage KE, Massari JV et al. (2005) Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood 105: 178-185

    Article  Google Scholar 

  • Pani G, Galeotti T, Chiarugi P (2010) Metastasis: cancer cell’s escape from oxidative stress. Cancer metastasis reviews 29: 351-378

    Article  Google Scholar 

  • Parekh A, Ruppender NS, Branch KM et al. (2011) Sensing and modulation of invadopodia across a wide range of rigidities. Biophys J 100: 573-582

    Article  Google Scholar 

  • Pavlides S, Whitaker-Menezes D, Castello-Cros R et al. (2009) The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle 8: 3984-4001

    Article  Google Scholar 

  • Peinado H, Aleckovic M, Lavotshkin S et al. (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18: 883-891

    Article  Google Scholar 

  • Peinado H, Ballestar E, Esteller M et al. (2004) Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex. Molecular and cellular biology 24: 306-319

    Article  Google Scholar 

  • Prime SS, Davies M, Pring M et al. (2004) The role of TGF-beta in epithelial malignancy and its relevance to the pathogenesis of oral cancer (part II). Crit Rev Oral Biol Med 15: 337-347

    Article  Google Scholar 

  • Rifkin DB, Sheppard D (1999) The integrin v 6 binds and activates latent TGF 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 96: 319-328

    Article  Google Scholar 

  • Schwartz MA (2010) Integrins and extracellular matrix in mechanotransduction. Cold Spring Harb Perspect Biol 2: a005066

    Article  Google Scholar 

  • Seoane J (2006) Escaping from the TGFbeta anti-proliferative control. Carcinogenesis 27: 2148-2156

    Article  Google Scholar 

  • Strell C, Entschladen F (2008) Extravasation of leukocytes in comparison to tumor cells. Cell Commun Signal 6: 10

    Article  Google Scholar 

  • Takeda K, Sakai N, Shiba H et al. (2011) Characteristics of high-molecular-weight hyaluronic acid as a brain-derived neurotrophic factor scaffold in periodontal tissue regeneration. Tissue engineering Part A 17: 955-967

    Article  Google Scholar 

  • ten Dijke P, Hill CS (2004) New insights into TGF-beta-Smad signalling. Trends Biochem Sci 29: 265-273

    Article  Google Scholar 

  • Thomas SN, Zhu F, Schnaar RL et al. (2008) Carcinoembryonic antigen and CD44 variant isoforms cooperate to mediate colon carcinoma cell adhesion to E- and L-selectin in shear flow. J Biol Chem 283: 15647-15655

    Article  Google Scholar 

  • Vong S, Kalluri R (2011) The role of stromal myofibroblast and extracellular matrix in tumor angiogenesis. Genes Cancer 2: 1139-1145

    Article  Google Scholar 

  • Wang G, Wang S, Li Y et al. (2013) Clinical study of disseminated tumor cells in bone marrow of patients with gastric cancer. Hepatogastroenterology 60: 273-276

    Google Scholar 

  • Wang HS, Tung WH, Tang KT et al. (2005) TGF-beta induced hyaluronan synthesis in orbital fibroblasts involves protein kinase C betaII activation in vitro. Journal of cellular biochemistry 95: 256-267

    Article  Google Scholar 

  • Wang J, Rong W, Hu X et al. (2012) Hyaluronan tetrasaccharide in the cerebrospinal fluid is associated with self-repair of rats after chronic spinal cord compression. Neuroscience 210: 467-480

    Article  Google Scholar 

  • Warburg O (1966) The Prime Cause and Prevention of Cancer.

    Google Scholar 

  • Waris G, Ahsan H (2006) Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinog 5: 14

    Article  Google Scholar 

  • Ween MP, Oehler MK, Ricciardelli C (2011) Role of Versican, Hyaluronan and CD44 in Ovarian Cancer Metastasis. Int J Mol Sci 12: 1009-1029

    Article  Google Scholar 

  • Wikman H, Vessella R, Pantel K (2008) Cancer micrometastasis and tumour dormancy. APMIS 116: 754-770

    Article  Google Scholar 

  • Wipff PJ, Rifkin DB, Meister JJ et al. (2007) Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix. The Journal of cell biology 179: 1311-1323

    Article  Google Scholar 

  • Wong SY, Hynes RO (2006) Lymphatic or hematogenous dissemination: how does a metastatic tumor cell decide? Cell Cycle 5: 812-817

    Article  Google Scholar 

  • Xian X, Hakansson J, Stahlberg A et al. (2006) Pericytes limit tumor cell metastasis. The Journal of clinical investigation 116: 642-651

    Article  Google Scholar 

  • Xu J, Lamouille S, Derynck R (2009) TGF-beta-induced epithelial to mesenchymal transition. Cell Res 19: 156-172

    Article  Google Scholar 

  • Yu Q, Stamenkovic I (2000) Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-β and promotes tumor invasion and angiogenesis. Genes & development 14: 163-176

    Google Scholar 

  • Zhang YE (2009) Non-Smad pathways in TGF-beta signaling. Cell Res 19: 128-139

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA

    Ying Xu & David Puett

  2. Department of Computer Science and Engineering, University of Nebraska, Lincoln, NE, USA

    Juan Cui

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  1. Ying Xu
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  2. Juan Cui
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Appendix

Appendix

Table 10.1 Data used for gene-expression analysis of circulating tumor cells
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Table 10.2 Data used for gene-expression analysis for Fig. 10.5
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Table 10.3 Data used for gene-expression analysis for Fig. 10.6
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Xu, Y., Cui, J., Puett, D. (2014). Understanding Cancer Invasion and Metastasis. In: Cancer Bioinformatics. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1381-7_10

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