Skip to main content
SpringerLink
Log in
Book cover

Cancer Targeted Drug Delivery pp 435–458Cite as

Mechanisms of Metastasis

  • Chapter
  • First Online:

Abstract

Metastatic disease is the culmination of cancer and its most common life-threatening manifestation. The highly complex process by which cancer cells disseminate to and successfully colonize organs distant from the primary tumor has been divided into stages, collectively termed the metastatic cascade. Decades of research into metastasis biology has yielded several proposed models, each of which address experimental and clinical observations and contribute mechanistic insight to the metastatic cascade. Despite major advances in dissecting and identifying associated molecular pathways, many details remain to be clarified about the mechanisms that enable tumor cells to form these life-threatening lesions. The lack of a comprehensive understanding of the mechanisms of metastasis has thus delayed advancement of therapeutic strategies for late stage cancer. Here, we review the leading models describing tumor progression and provide an overview of the current state of the scientific community’s understanding of metastasis.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29

    Article  PubMed  Google Scholar 

  2. Leber MF, Efferth T (2009) Molecular principles of cancer invasion and metastasis (review). Int J Oncol 34:881–895

    CAS  PubMed  Google Scholar 

  3. Valastyan S, Weinberg RA (2011) Tumor metastasis: molecular insights and evolving paradigms. Cell 147:275–292

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Lu X, Kang Y (2007) Organotropism of breast cancer metastasis. J Mammary Gland Biol Neoplasia 12:153–162

    Article  PubMed  Google Scholar 

  5. Minn AJ, Kang Y, Serganova I, Gupta GP, Giri DD, Doubrovin M, Ponomarev V, Gerald WL, Blasberg R, Massague J (2005) Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J Clin Invest 115:44–55

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Fidler IJ (1970) Metastasis: guantitative analysis of distribution and fate of tumor embolilabeled with 125 I-5-iodo-2′-deoxyuridine. J Natl Cancer Inst 45:773–782

    CAS  PubMed  Google Scholar 

  7. Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194:23–28

    Article  CAS  PubMed  Google Scholar 

  8. Talmadge JE (2007) Clonal selection of metastasis within the life history of a tumor. Cancer Res 67:11471–11475

    Article  CAS  PubMed  Google Scholar 

  9. Ruiz C, Lenkiewicz E, Evers L, Holley T, Robeson A, Kiefer J, Demeure MJ, Hollingsworth MA, Shen M, Prunkard D, Rabinovitch PS, Zellweger T, Mousses S, Trent JM, Carpten JD, Bubendorf L, Von Hoff D, Barrett MT (2011) Advancing a clinically relevant perspective of the clonal nature of cancer. Proc Natl Acad Sci USA 108:12054–12059

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Fidler IJ, Kripke ML (1977) Metastasis results from preexisting variant cells within a malignant tumor. Science 197:893–895

    Article  CAS  PubMed  Google Scholar 

  11. Fidler IJ, Talmadge JE (1986) Evidence that intravenously derived murine pulmonary melanoma metastases can originate from the expansion of a single tumor cell. Cancer Res 46:5167–5171

    CAS  PubMed  Google Scholar 

  12. Wu X, Northcott PA, Dubuc A, Dupuy AJ, Shih DJ, Witt H, Croul S, Bouffet E, Fults DW, Eberhart CG, Garzia L, Van Meter T, Zagzag D, Jabado N, Schwartzentruber J, Majewski J, Scheetz TE, Pfister SM, Korshunov A, Li XN, Scherer SW, Cho YJ, Akagi K, MacDonald TJ, Koster J, McCabe MG, Sarver AL, Collins VP, Weiss WA, Largaespada DA, Collier LS, Taylor MD (2012) Clonal selection drives genetic divergence of metastatic medulloblastoma. Nature 482:529–533

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Lo Nigro C, Vivenza D, Monteverde M, Lattanzio L, Gojis O, Garrone O, Comino A, Merlano M, Quinlan PR, Syed N, Purdie CA, Thompson A, Palmieri C, Crook T (2012) High frequency of complex TP53 mutations in CNS metastases from breast cancer. Br J Cancer 106:397–404

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Mahale AM, Khan ZA, Igarashi M, Nanjangud GJ, Qiao RF, Yao S, Lee SW, Aaronson SA (2008) Clonal selection in malignant transformation of human fibroblasts transduced with defined cellular oncogenes. Cancer Res 68:1417–1426

    Article  CAS  PubMed  Google Scholar 

  15. Montemurro F, Sarotto I, Casorzo L, Pisacane A, Aglietta M, De Rosa G (2004) HER2 and central nervous system metastasis in patients with breast cancer. Clin Breast Cancer 5:232–234

    Article  PubMed  Google Scholar 

  16. Daves MH, Hilsenbeck SG, Lau CC, Man TK (2011) Meta-analysis of multiple microarray datasets reveals a common gene signature of metastasis in solid tumors. BMC Med Genomics 4:56

    Article  PubMed Central  PubMed  Google Scholar 

  17. Khalique L, Ayhan A, Whittaker JC, Singh N, Jacobs IJ, Gayther SA, Ramus SJ (2009) The clonal evolution of metastases from primary serous epithelial ovarian cancers. Int J Cancer 124:1579–1586

    Article  CAS  PubMed  Google Scholar 

  18. Brosnan JA, Iacobuzio-Donahue CA (2012) A new branch on the tree: next-generation sequencing in the study of cancer evolution. Semin Cell Dev Biol 23:237–242

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Ding L, Ellis MJ, Li S, Larson DE, Chen K, Wallis JW, Harris CC, McLellan MD, Fulton RS, Fulton LL, Abbott RM, Hoog J, Dooling DJ, Koboldt DC, Schmidt H, Kalicki J, Zhang Q, Chen L, Lin L, Wendl MC, McMichael JF, Magrini VJ, Cook L, McGrath SD, Vickery TL, Appelbaum E, Deschryver K, Davies S, Guintoli T, Crowder R, Tao Y, Snider JE, Smith SM, Dukes AF, Sanderson GE, Pohl CS, Delehaunty KD, Fronick CC, Pape KA, Reed JS, Robinson JS, Hodges JS, Schierding W, Dees ND, Shen D, Locke DP, Wiechert ME, Eldred JM, Peck JB, Oberkfell BJ, Lolofie JT, Du F, Hawkins AE, O'Laughlin MD, Bernard KE, Cunningham M, Elliott G, Mason MD, Thompson DM Jr, Ivanovich JL, Goodfellow PJ, Perou CM, Weinstock GM, Aft R, Watson M, Ley TJ, Wilson RK, Mardis ER (2010) Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 464:999–1005

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, Cook K, Stepansky A, Levy D, Esposito D, Muthuswamy L, Krasnitz A, McCombie WR, Hicks J, Wigler M (2011) Tumour evolution inferred by single-cell sequencing. Nature 472:90–94

    Article  CAS  PubMed  Google Scholar 

  21. 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 5:744–749

    Article  CAS  PubMed  Google Scholar 

  22. Weigelt B, Glas AM, Wessels LF, Witteveen AT, Peterse JL, van't Veer LJ (2003) Gene expression profiles of primary breast tumors maintained in distant metastases. Proc Natl Acad Sci USA 100:15901–15905

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Van’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:530–536

    Article  Google Scholar 

  24. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111

    Article  CAS  PubMed  Google Scholar 

  25. Furusawa C, Kaneko K (2012) A dynamical-systems view of stem cell biology. Science 338:215–217

    Article  CAS  PubMed  Google Scholar 

  26. Chaffer CL, Weinberg RA (2011) A perspective on cancer cell metastasis. Science 331:1559–1564

    Article  CAS  PubMed  Google Scholar 

  27. Brabletz T (2012) To differentiate or not–routes towards metastasis. Nat Rev Cancer 12:425–436

    Article  CAS  PubMed  Google Scholar 

  28. Li F, Tiede B, Massague J, Kang Y (2007) Beyond tumorigenesis: cancer stem cells in metastasis. Cell Res 17:3–14

    Article  CAS  PubMed  Google Scholar 

  29. Li L, Neaves WB (2006) Normal stem cells and cancer stem cells: the niche matters. Cancer Res 66:4553–4557

    Article  CAS  PubMed  Google Scholar 

  30. Dick JE (2008) Stem cell concepts renew cancer research. Blood 112:4793–4807

    Article  CAS  PubMed  Google Scholar 

  31. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. 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 1:313–323

    Article  CAS  PubMed  Google Scholar 

  33. 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 445:111–115

    Article  CAS  PubMed  Google Scholar 

  34. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951

    Article  CAS  PubMed  Google Scholar 

  35. Davies JA (1996) Mesenchyme to epithelium transition during development of the mammalian kidney tubule. Acta Anat 156:187–201

    Article  CAS  PubMed  Google Scholar 

  36. Hay ED (2005) The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it. Dev Dyn 233:706–720

    Article  CAS  PubMed  Google Scholar 

  37. 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 133:704–715

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Gunasinghe NP, Wells A, Thompson EW, Hugo HJ (2012) Mesenchymal-epithelial transition (MET) as a mechanism for metastatic colonisation in breast cancer. Cancer Metastasis Rev 31:469–478

    Article  CAS  PubMed  Google Scholar 

  39. Mendez MG, Kojima S, Goldman RD (2010) Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition. FASEB J 24:1838–1851

    Article  CAS  PubMed  Google Scholar 

  40. Deryugina EI, Quigley JP (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25:9–34

    Article  CAS  PubMed  Google Scholar 

  41. Weiss L (1990) Metastatic inefficiency. Adv Cancer Res 54:159–211

    CAS  PubMed  Google Scholar 

  42. Ishikawa M, Okada F, Hamada J, Hosokawa M, Kobayashi H (1987) Changes in the tumorigenic and metastatic properties of tumor cells treated with quercetin or 5-azacytidine. Int J Cancer 39:338–342

    Article  CAS  PubMed  Google Scholar 

  43. Olsson L, Forchhammer J (1984) Induction of the metastatic phenotype in a mouse tumor model by 5-azacytidine, and characterization of an antigen associated with metastatic activity. Proc Natl Acad Sci USA 81:3389–3393

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Stopper H, Pechan R, Schiffmann D (1992) 5-azacytidine induces micronuclei in and morphological transformation of Syrian hamster embryo fibroblasts in the absence of unscheduled DNA synthesis. Mutat Res 283:21–28

    Article  CAS  PubMed  Google Scholar 

  45. Trainer DL, Kline T, Hensler G, Greig R, Poste G (1988) Clonal analysis of the malignant properties of B16 melanoma cells treated with the DNA hypomethylating agent 5-azacytidine. Clin Exp Metastasis 6:185–200

    Article  CAS  PubMed  Google Scholar 

  46. Kerbel RS, Frost P, Liteplo R, Carlow DA, Elliott BE (1984) Possible epigenetic mechanisms of tumor progression: induction of high-frequency heritable but phenotypically unstable changes in the tumorigenic and metastatic properties of tumor cell populations by 5-azacytidine treatment. J Cell Physiol Suppl 3:87–97

    Article  CAS  PubMed  Google Scholar 

  47. Chambers AF, Wilson S (1988) Use of NeoR B16F1 murine melanoma cells to assess clonality of experimental metastases in the immune-deficient chick embryo. Clin Exp Metastasis 6:171–182

    Article  CAS  PubMed  Google Scholar 

  48. Cheung ST, Chen X, Guan XY, Wong SY, Tai LS, Ng IO, So S, Fan ST (2002) Identify metastasis-associated genes in hepatocellular carcinoma through clonality delineation for multinodular tumor. Cancer Res 62:4711–4721

    CAS  PubMed  Google Scholar 

  49. Fidler IJ, Yano S, Zhang RD, Fujimaki T, Bucana CD (2002) The seed and soil hypothesis: vascularisation and brain metastases. Lancet Oncol 3:53–57

    Article  CAS  PubMed  Google Scholar 

  50. Fidler IJ, Hart IR (1981) The origin of metastatic heterogeneity in tumors. Eur J Cancer 17:487–494

    Article  CAS  PubMed  Google Scholar 

  51. Poste G, Tzeng J, Doll J, Greig R, Rieman D, Zeidman I (1982) Evolution of tumor cell heterogeneity during progressive growth of individual lung metastases. Proc Natl Acad Sci USA 79:6574–6578

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Helft J, Ginhoux F, Bogunovic M, Merad M (2010) Origin and functional heterogeneity of non-lymphoid tissue dendritic cells in mice. Immunol Rev 234:55–75

    Article  CAS  PubMed  Google Scholar 

  53. Pawelek JM, Chakraborty AK (2008) Fusion of tumour cells with bone marrow-derived cells: a unifying explanation for metastasis. Nat Rev Cancer 8:377–386

    Article  CAS  PubMed  Google Scholar 

  54. Pawelek JM, Chakraborty AK (2008) The cancer cell–leukocyte fusion theory of metastasis. Adv Cancer Res 101:397–444

    CAS  PubMed  Google Scholar 

  55. Goldenberg DM, Pavia RA, Tsao MC (1974) In vivo hybridisation of human tumour and normal hamster cells. Nature 250:649–651

    Article  CAS  PubMed  Google Scholar 

  56. Larizza L, Schirrmacher V, Graf L, Pfluger E, Peres-Martinez M, Stohr M (1984) Suggestive evidence that the highly metastatic variant ESb of the T-cell lymphoma Eb is derived from spontaneous fusion with a host macrophage. Int J Cancer 34:699–707

    Article  CAS  PubMed  Google Scholar 

  57. Carloni V, Mazzocca A, Mello T, Galli A, Capaccioli S (2012) Cell fusion promotes chemoresistance in metastatic colon carcinoma. Oncogene 32(21):2649–2660

    Google Scholar 

  58. De Baetselier P, Roos E, Brys L, Remels L, Gobert M, Dekegel D, Segal S, Feldman M (1984) Nonmetastatic tumor cells acquire metastatic properties following somatic hybridization with normal cells. Cancer Metastasis Rev 3:5–24

    Article  PubMed  Google Scholar 

  59. Chakraborty A, Lazova R, Davies S, Backvall H, Ponten F, Brash D, Pawelek J (2004) Donor DNA in a renal cell carcinoma metastasis from a bone marrow transplant recipient. Bone Marrow Transplant 34:183–186

    Article  CAS  PubMed  Google Scholar 

  60. Yilmaz Y, Lazova R, Qumsiyeh M, Cooper D, Pawelek J (2005) Donor Y chromosome in renal carcinoma cells of a female BMT recipient: visualization of putative BMT-tumor hybrids by FISH. Bone Marrow Transplant 35:1021–1024

    Article  CAS  PubMed  Google Scholar 

  61. Bendich A, Wilczok T, Borenfreund E (1965) Circulating DNA as a possible factor in oncogenesis. Science 148:374–376

    Article  CAS  PubMed  Google Scholar 

  62. Leon SA, Shapiro B, Sklaroff DM, Yaros MJ (1977) Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res 37:646–650

    CAS  PubMed  Google Scholar 

  63. Garcia-Olmo DC, Ruiz-Piqueras R, Garcia-Olmo D (2004) Circulating nucleic acids in plasma and serum (CNAPS) and its relation to stem cells and cancer metastasis: state of the issue. Histol Histopathol 19:575–583

    CAS  PubMed  Google Scholar 

  64. Schwarzenbach H, Hoon DS, Pantel K (2011) Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 11:426–437

    Article  CAS  PubMed  Google Scholar 

  65. Widschwendter M, Menon U (2006) Circulating methylated DNA: a new generation of tumor markers. Clin Cancer Res 12:7205–7208

    Article  CAS  PubMed  Google Scholar 

  66. Berezikov E (2011) Evolution of microRNA diversity and regulation in animals. Nat Rev Genet 12:846–860

    Article  CAS  PubMed  Google Scholar 

  67. Huang Y, Shen XJ, Zou Q, Wang SP, Tang SM, Zhang GZ (2011) Biological functions of microRNAs: a review. J Physiol Biochem 67:129–139

    Article  CAS  PubMed  Google Scholar 

  68. Aigner A (2011) MicroRNAs (miRNAs) in cancer invasion and metastasis: therapeutic approaches based on metastasis-related miRNAs. J Mol Med (Berl) 89:445–457

    Article  CAS  Google Scholar 

  69. Nicoloso MS, Spizzo R, Shimizu M, Rossi S, Calin GA (2009) MicroRNAs—the micro steering wheel of tumour metastases. Nat Rev Cancer 9:293–302

    Article  CAS  PubMed  Google Scholar 

  70. Hoon DS, Ferris R, Tanaka R, Chong KK, Alix-Panabieres C, Pantel K (2011) Molecular mechanisms of metastasis. J Surg Oncol 103:508–517

    Article  CAS  PubMed  Google Scholar 

  71. Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65:6029–6033

    Article  CAS  PubMed  Google Scholar 

  72. Pagliuca A, Valvo C, Fabrizi E, di Martino S, Biffoni M, Runci D, Forte S, De Maria R, Ricci-Vitiani L (2012) Analysis of the combined action of miR-143 and miR-145 on oncogenic pathways in colorectal cancer cells reveals a coordinate program of gene repression. Oncogene, pp 1–8

    Google Scholar 

  73. Liu ZL, Wang H, Liu J, Wang ZX (2012) MicroRNA-21 (miR-21) expression promotes growth, metastasis, and chemo- or radioresistance in non-small cell lung cancer cells by targeting PTEN. Mol Cell Biochem 372(1–2):35–45

    PubMed  Google Scholar 

  74. Deng JH, Deng Q, Kuo CH, Delaney SW, Ying SY (2013) MiRNA targets of prostate cancer. Methods Mol Biol 936:357–369

    Article  CAS  PubMed  Google Scholar 

  75. Edmonds MD, Hurst DR, Vaidya KS, Stafford LJ, Chen D, Welch DR (2009) Breast cancer metastasis suppressor 1 coordinately regulates metastasis-associated microRNA expression. Int J Cancer 125:1778–1785

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Zhu S, Si ML, Wu H, Mo YY (2007) MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 282:14328–14336

    Article  CAS  PubMed  Google Scholar 

  77. Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449:682–688

    Article  CAS  PubMed  Google Scholar 

  78. Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, Egan DA, Li A, Huang G, Klein-Szanto AJ, Gimotty PA, Katsaros D, Coukos G, Zhang L, Pure E, Agami R (2008) The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol 10:202–210

    Article  CAS  PubMed  Google Scholar 

  79. Png KJ, Halberg N, Yoshida M, Tavazoie SF (2012) A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature 481:190–194

    Article  CAS  Google Scholar 

  80. Hao NB, Lu MH, Fan YH, Cao YL, Zhang ZR, Yang SM (2012) Macrophages in tumor microenvironments and the progression of tumors. Clin Dev Immunol 2012:948098

    Article  PubMed Central  PubMed  Google Scholar 

  81. Bhowmick NA, Neilson EG, Moses HL (2004) Stromal fibroblasts in cancer initiation and progression. Nature 432:332–337

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev Cancer 9:239–252

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  83. Mintz B, Illmensee K (1975) Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci USA 72:3585–3589

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Hayward SW, Wang Y, Cao M, Hom YK, Zhang B, Grossfeld GD, Sudilovsky D, Cunha GR (2001) Malignant transformation in a nontumorigenic human prostatic epithelial cell line. Cancer Res 61:8135–8142

    CAS  PubMed  Google Scholar 

  85. Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR (1999) Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res 59:5002–5011

    CAS  PubMed  Google Scholar 

  86. Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, Zhu Z, 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 438:820–827

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Ge R, Tan E, Sharghi-Namini S, Asada HH (2012) Exosomes in cancer microenvironment and beyond: have we overlooked these extracellular messengers? Cancer Microenviron 5:323–332

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Taylor DD, Gercel-Taylor C (2011) Exosomes/microvesicles: mediators of cancer-associated immunosuppressive microenvironments. Semin Immunopathol 33:441–454

    Article  CAS  PubMed  Google Scholar 

  89. Peinado H, Aleckovic M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, Garcia-Santos G, Ghajar C, Nitadori-Hoshino A, Hoffman C, Badal K, Garcia BA, Callahan MK, Yuan J, Martins VR, Skog J, Kaplan RN, Brady MS, Wolchok JD, Chapman PB, Kang Y, Bromberg J, Lyden D (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18:883–891

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  90. Hunter K (2006) Host genetics influence tumour metastasis. Nat Rev Cancer 6:141–146

    Article  CAS  PubMed  Google Scholar 

  91. Krimpenfort P, Quon KC, Mooi WJ, Loonstra A, Berns A (2001) Loss of p16Ink4a confers susceptibility to metastatic melanoma in mice. Nature 413:83–86

    Article  CAS  PubMed  Google Scholar 

  92. Crawford NP, Ziogas A, Peel DJ, Hess J, Anton-Culver H, Hunter KW (2006) Germline polymorphisms in SIPA1 are associated with metastasis and other indicators of poor prognosis in breast cancer. Breast Cancer Res 8:R16

    Article  PubMed Central  PubMed  Google Scholar 

  93. Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, Taite H, Scoular R, Miller A, Reeve AE (1998) E-cadherin germline mutations in familial gastric cancer. Nature 392:402–405

    Article  CAS  PubMed  Google Scholar 

  94. Francia G, Cruz-Munoz W, Man S, Xu P, Kerbel RS (2011) Mouse models of advanced spontaneous metastasis for experimental therapeutics. Nat Rev Cancer 11:135–141

    Article  CAS  PubMed  Google Scholar 

  95. Park YG, Zhao X, Lesueur F, Lowy DR, Lancaster M, Pharoah P, Qian X, Hunter KW (2005) Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1. Nat Genet 37:1055–1062

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  96. Yang H, Crawford N, Lukes L, Finney R, Lancaster M, Hunter KW (2005) Metastasis predictive signature profiles pre-exist in normal tissues. Clin Exp Metastasis 22:593–603

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  97. Hu Y, Wu G, Rusch M, Lukes L, Buetow KH, Zhang J, Hunter KW (2012) Integrated cross-species transcriptional network analysis of metastatic susceptibility. Proc Natl Acad Sci USA 109:3184–3189

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  98. Faraji F, Pang Y, Walker RC, Nieves Borges R, Yang L, Hunter KW (2012) Cadm1 is a metastasis susceptibility gene that suppresses metastasis by modifying tumor interaction with the cell-mediated immunity. PLoS Genet 8:e1002926

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Winter SF, Lukes L, Walker RC, Welch DR, Hunter KW (2012) Allelic variation and differential expression of the mSIN3A histone deacetylase complex gene Arid4b promote mammary tumor growth and metastasis. PLoS Genet 8:e1002735

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Institutes of Health, NCI, Center for Cancer Research, Intramural Research Program.

Author information

Authors and Affiliations

  1. Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA

    Ngoc-Han Ha & Farhoud Faraji

  2. Laboratory of Cancer Biology and Genetics, Metastasis Susceptibility Section, Center for Cancer Research, National Cancer Institute, NIH, Building 37, Room 5046C, 37 Convent Drive, Bethesda, MD, 20892-4264, USA

    Kent W. Hunter Ph.D.

Authors
  1. Ngoc-Han Ha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Farhoud Faraji
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kent W. Hunter Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kent W. Hunter Ph.D. .

Editor information

Editors and Affiliations

  1. Pharmacutics & Pharmacutical Chemistry, University of Utah, Salt Lake City, Utah, USA

    You Han Bae

  2. Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath, United Kingdom

    Randall J. Mrsny

  3. Department of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA

    Kinam Park

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Ha, NH., Faraji, F., Hunter, K.W. (2013). Mechanisms of Metastasis. In: Bae, Y., Mrsny, R., Park, K. (eds) Cancer Targeted Drug Delivery. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7876-8_17

Download citation

Publish with us

Policies and ethics

Search

Navigation