Skip to main content
SpringerLink
Log in

Cancer Metastasis

  • Chapter
Oncology

Abstract

ancer metastasis, the spread of cancer from its primary location to secondary sites, heralds the progression to a fundamentally distinct oncologic disease. Metastatic infiltration often disrupts the integrity and physiologic functioning of the target organ, giving rise to the pain, morbidity, and mortality that make metastatic disease such a devastating illness.

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

Access this chapter

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 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
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

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Chang HM. Cancer pain management. Med Clin N Am 1999;83:711–736.

    Article  PubMed  CAS  Google Scholar 

  2. Cleeland CS, et al. Pain and its treatment in outpatients with metastatic cancer. N Engl J Med 1994;330:592–596.

    Article  PubMed  CAS  Google Scholar 

  3. Perron V, Schonwetter RS. Assessment and management of pain in palliative care patients. Cancer Control 2001:8:15–24.

    PubMed  CAS  Google Scholar 

  4. El Kamar FG, Grossbard ML, Kozuch PS. Metastatic pancreatic cancer: emerging strategies in chemotherapy and palliative care. Oncologist 2003;8:18–34.

    Article  PubMed  Google Scholar 

  5. Brescia FJ, Portenoy RK, Ryan M, Krasnoff L, Gray G. Pain, opiod use, and survival in hospitalized patients with advanced cancer. J Clin Oncol 1992;10:149–155.

    PubMed  CAS  Google Scholar 

  6. Sporin MB. The war on cancer. Lancet 1996;347:1377–1381.

    Article  Google Scholar 

  7. Woodhouse EC, Chuaqui RF, Liotta LA. General mechanisms of metastasis. Cancer (Phila) 1997;80:1529–1537.

    Article  PubMed  CAS  Google Scholar 

  8. Fidler IJ. Critical determinants of metastasis. Cancer Biol 2002;12:89–96.

    Article  Google Scholar 

  9. Weir HK, et al. Annual report to the nation on the status of cancer, 1975–2000, featuring the uses of surveillance data for cancer prevention and control. JNCI 2003;95:1276–1299.

    PubMed  Google Scholar 

  10. Glare P, et al. A systemic review of physician’s survival predictions in terminally ill cancer patients. BMJ 2003;327:1–6.

    Article  Google Scholar 

  11. Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2002;2:563–572.

    Article  PubMed  CAS  Google Scholar 

  12. Hanahan D, Weinberg A. The hallmarks of cancer. Cell 2000;100:57–70.

    Article  PubMed  CAS  Google Scholar 

  13. Hahn WC, Weinberg RA. Rules for making human tumor cells. N Engl J Med 2002;347:1593–1603.

    Article  PubMed  CAS  Google Scholar 

  14. Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature (Lond) 1998;396:643–649.

    Article  PubMed  CAS  Google Scholar 

  15. Papadopoulos S, et al. Assessment of genomic instability in breast cancer and uveal melanoma by random amplified polymorphic DNA analysis. Int J Cancer 2002;99:193–200.

    Article  PubMed  CAS  Google Scholar 

  16. Vineis P, Matullo G, Manuguerra M. An evolutionary paradigm for carcinogenesis. J Epidemiol Community Health 2003;57:89–95.

    Article  PubMed  CAS  Google Scholar 

  17. Gatenby RA, Vicent TL. An evolutionary model of carcinogenesis. Cancer Res 2003;63:6212–6220.

    PubMed  CAS  Google Scholar 

  18. Vineis P. Cancer as an evolutionary process at the cell level: an epidemiological perspective. Carcinogenesis (Oxf) 2003;24:1–6.

    Article  PubMed  CAS  Google Scholar 

  19. Pozzatti R, et al. Primary rat embryo cells transformed by one or two oncogenes show different metastatic potentials. Science 1986;232:223–227.

    Article  PubMed  CAS  Google Scholar 

  20. Wyllie A, et al. Rodent fibroblast tumors expressing human myc and ras genes: growth, metastasis and endogenous oncogene expression. Br J Cancer 1987;56:251–259.

    PubMed  CAS  Google Scholar 

  21. Steeg PS. Metastatic suppressors alter the signal transduction of cancer cells. Nat Rev Cancer 2002;3:55–63.

    Article  CAS  Google Scholar 

  22. Shevde LA, Welch DR. Metastasis suppressor pathways—an evolving paradigm. Cancer Lett 2003;198:1–20.

    Article  PubMed  CAS  Google Scholar 

  23. Steeg PS, et al. Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst 1988;80:200–204.

    Article  PubMed  CAS  Google Scholar 

  24. Steeg PS, Palmieri T, Ouatas M, Salerno M. Histidine kinases and histidine phosphorylated proteins in mammalian cell biology, signal transduction and cancer. Cancer Lett 2003;190:1–12.

    Article  PubMed  CAS  Google Scholar 

  25. Chikawa T, et al. Localization of metastasis suppressor gene(s) for prostatic cancer to the short arm of human chromosone 11. Cancer Res 1992;52:3486–3490.

    Google Scholar 

  26. Lee JH, et al. KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst 1996;88:1731–1737.

    Article  PubMed  CAS  Google Scholar 

  27. Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2002;2:161–174.

    Article  PubMed  CAS  Google Scholar 

  28. Yamada SD, et al. Mitogen-activated protein kinase kinase 4 (MKK4) acts as a metastasis suppressor gene in human ovarian carcinoma. Cancer Res 2002;62:6717–6723.

    PubMed  CAS  Google Scholar 

  29. Kauffman EC, Robinson VL, Stadler WM, Sokoloff MH, Rinker-Schaeffer CW. Metastasis suppression: the evolving role of metastasis suppressor genes for regulating cancer cell growth at the secondary site. J Urol 2003;169:1122–1133.

    Article  PubMed  Google Scholar 

  30. Seraj MJ, Samant RS, Verderame MF, Welch DR. Functional evidence for a novel human breast carcinoma metastasis suppressor, BRMS1, encoded at chromosome 11q13. Cancer Res 2000;60:2764–2769.

    PubMed  CAS  Google Scholar 

  31. Xia W, Unger P, Miller L, Nelson J, Gelman IH. The Src-suppressed C kinase substrate, SSeCKS, is a potential metastasis inhibitor in prostate cancer. Cancer Res 2001;61:5644–5651.

    PubMed  CAS  Google Scholar 

  32. Gildea JJ, et al. RhoGD12 is an invasion and metastasis suppressor gene in human cancer. Cancer Res 2002;62:6418–6423.

    PubMed  CAS  Google Scholar 

  33. Bandyopadhyay S, et al. The Drg-1 gene suppresses tumor metastasis in prostate cancer. Cancer Res 2003;63:1731–1736.

    PubMed  CAS  Google Scholar 

  34. Fidler IJ. The organ microenvironment and cancer metastasis. Differentiation (Camb) 2002;70:498–505.

    Article  PubMed  Google Scholar 

  35. Park CC, Bissell MJ, Baecellos-Hoff MH. The influence of the microenvironment on the malignant phenotype. Mol Med Today 2000;6:324–329.

    Article  PubMed  CAS  Google Scholar 

  36. Roskelley CD, Bissell MJ. The dominance of the microenvironment in breast and ovarian cancer. Cancer Biol 2002;12:97–104.

    Article  Google Scholar 

  37. Kinzler KW, Vogelstein B. Landscaping the cancer terrain. Science 1998;280:1036–1037.

    Article  PubMed  CAS  Google Scholar 

  38. Wang F, et al. Phenotypic reversion or death of cancer cells by altering signaling pathways in three dimensional contexts. JNCI 2002;94:1494–1503.

    PubMed  CAS  Google Scholar 

  39. Bissell MJ, Radisky D. Putting tumors in context. Nat Rev Cancer 2001;1:46–54.

    Article  PubMed  CAS  Google Scholar 

  40. Tisty TD, Hein PW. Know thy neighbor: stromal cells can contribute oncogenic signals. Curr Opin Genet Dev 2001;11:54–59.

    Article  Google Scholar 

  41. Skobe M, Fusenig NE. Tumorigenic conversion of immortal human keratinocytes through stromal cell activation. Proc Natl Acad Sci USA 1998;95:1050–1055.

    Article  PubMed  CAS  Google Scholar 

  42. Olumi AF, et al. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res 1999;59:5002–5011.

    PubMed  CAS  Google Scholar 

  43. Pardoll DM. Does the immune system see tumors as foreign or self? Annu Rev Immunol 2003;21:807–839.

    Article  PubMed  CAS  Google Scholar 

  44. Hadden JW. Immunodeficiency and cancer: prospects for correlation. Int Immunopharmacol 2003;3:1061–1071.

    Article  PubMed  CAS  Google Scholar 

  45. Mbulaiteye SM, Biggar RJ, Goedert JJ, Engels EA. Immune deficiency and risk for malignancy among persons with AIDS. J AIDS 2003;32:527–533.

    Google Scholar 

  46. Gruijl FR. Ultraviolet radiation and tumor immunity. Methods 2002;28:122–129.

    Article  PubMed  CAS  Google Scholar 

  47. Mudgil AD, et al. Ultraviolet B irradiation induces expansion of intraepithelial tumor cells in a tissue model of early cancer progression. J Invest Dermatol 2003;121:191–197.

    Article  PubMed  CAS  Google Scholar 

  48. Fisher MS, Kripke ML. Systemic alteration induced in mice by ultraviolet light irradiation and its relationship to ultraviolet carcinogenesis. Proc Natl Acad Sci USA 1977;74:1688–1692.

    Article  PubMed  CAS  Google Scholar 

  49. Jiang W, et al. UV irradiation augments lymphoid malignancies in mice with one functional copy of wild-type p53. Proc Natl Acad Sci USA 2001;98:9790–9795.

    Article  PubMed  CAS  Google Scholar 

  50. Schwartzbaum J, et al. Cohort studies of association between self-reported allergic conditions, immune-related diagnoses and glioma and meningioma risk. Int J Cancer 2003;106:423–428.

    Article  PubMed  CAS  Google Scholar 

  51. Holly EA, Eberle CA, Bracci PM. Prior history of allergies and pancreatic cancer in the San Francisco Bay Area. Am J Epidemiol 2003;158:432–441.

    Article  PubMed  Google Scholar 

  52. Maria DA, et al. Resistance to melanoma metastases in mice selected for high acute inflammatory response. Carcinogenesis (Oxf) 2001;22:337–342.

    Article  PubMed  CAS  Google Scholar 

  53. Cui Z, et al. Spontaneous regression of advanced cancer: identification of a unique genetically determined, age-dependent trait in mice. Proc Natl Acad Sci USA 2003;100:6682–6687.

    Article  PubMed  CAS  Google Scholar 

  54. Weidner N. Angiogenesis as a predictor of clinical outcome in cancer patients. Hum Pathol 2000;31:403–405.

    Article  PubMed  CAS  Google Scholar 

  55. Thompson WD. Tumour versus patient: vascular and tumour survival versus prognosis. J Pathol 2001;193:425–426.

    Article  PubMed  CAS  Google Scholar 

  56. Weidner N, Folkman J, Pozza F. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst 1992;84:1875–1887.

    Article  PubMed  CAS  Google Scholar 

  57. Toi M, Inada K, Suzuki H. Tumor angiogenesis in breast cancer: its importance as a prognostic indicator and association with vascular endothelial growth factor suppression. Breast Cancer Res Treat 1995;36:193–204.

    Article  PubMed  CAS  Google Scholar 

  58. Eppenberger U, Kueng W, Schlaeppi JM. Markers of tumor angiogenesis and proteolysis independently define high-and low-risk subsets of node-negative breast cancer patients. J Clin Oncol 1998:16:3129–3136.

    PubMed  CAS  Google Scholar 

  59. Bian XW, Du LL, Shi JQ. Correlation of bFGF, FGF-1 and VEGF expression with vascularity and malignancy of human astrocytomas. Anal Quant Cytol Histol 2000;22:267–274.

    PubMed  CAS  Google Scholar 

  60. Eggert A, Ikegaki N, Kwiatkowski J. High-level expression of angiogenic factors is associated with advanced tumor stage in human neuroblastomas. Clin Cancer Res 1999;6:1900–1908.

    Google Scholar 

  61. Stockhammer G, Obwegeser A, Kostron H. Vascular endothelial growth factor (VEGF) is elevated in brain tumor cysts and correlates with tumor progression. Acta Neuropathol (Berl) 2000;100:101–105.

    Article  PubMed  CAS  Google Scholar 

  62. Loncaster JA, Cooper RA, Logue JP. Vascular endothelial growth factor (VEGF) expression is a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. Br J Cancer 2000;83:775–781.

    Article  Google Scholar 

  63. Hollingsworth HC, Kohn EC, Steinberg SM, Rothenberg ML, Meriono MJ. Tumor angiogenesis in advanced stage ovarian carcinoma. Am J Pathol 1995;147:33.

    PubMed  CAS  Google Scholar 

  64. Sivridis E, Giatromanolaki A, Gatter KC, Harris AL, Koukourakis MI. Association of hypoxia inducible factor 1-alpha and 2-alpha with activated angiogenic pathways and prognosis in patients with endometrial carcinomas. Cancer (Phila) 2002;95:1055–1063.

    Article  PubMed  CAS  Google Scholar 

  65. Yoshikawa T, Tsuburaya A, Kobayashi O. Plasma concentrations of VEGF and bFGF in patients with gastric carcinoma. Cancer Lett 2000;153:7–12.

    Article  PubMed  CAS  Google Scholar 

  66. Cascinu S, Staccioli MP, Gasparini G. Expression of vascular endothelial growth factor can predict event-free survival in stage II colon cancer. Clin Cancer Res 2000:2803–2807.

    Google Scholar 

  67. Maeda K, Chung Y, Takatsuka S. Tumour angiogenesis and tumour cell proliferation as prognostic indicators in gastric carcinoma. Br J Cancer 1995;72:319.

    PubMed  CAS  Google Scholar 

  68. Weidner N, Carroll PR, Flax J. Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol 1993;143:401–409.

    PubMed  CAS  Google Scholar 

  69. Fregene TA, Khanuja PS, Noto AC. Tumor-associated angiogenesis in prostate cancer. Anticancer Res 1993;13:2377.

    PubMed  CAS  Google Scholar 

  70. Liotta LA, Kleinerman J, Saidel G. Quantitative relationships of intravascular tumor cells, tumor vessels and pulmonary metastases following tumor implantation. Cancer Res 1974;34:997–1004.

    PubMed  CAS  Google Scholar 

  71. Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol 2002;29:15–18.

    PubMed  CAS  Google Scholar 

  72. Carmeliet P. Angiogenesis in cancer and other diseases. Nature (Lond) 2000;407:249–257.

    Article  PubMed  CAS  Google Scholar 

  73. Detmar M, Velasco P, Richard L. Expression of vascular endothelial growth factor induces an invasive phenotype in human squamous cell carcinomas. Am J Pathol 2000;156:159–167.

    PubMed  CAS  Google Scholar 

  74. Ribatti D, Vacca A, Dammacco F. The role of vascular phase in solid tumor growth: a historical review. Neoplasia 1999;1:293–302.

    Article  PubMed  CAS  Google Scholar 

  75. Folkman J. Angiogenesis and apoptosis. Semin Cancer Biol 2003;13:159–167.

    Article  PubMed  CAS  Google Scholar 

  76. Zetter BR. Angiogenesis and tumor metastasis. Annu Rev Med 1998;49:407–424.

    Article  PubMed  CAS  Google Scholar 

  77. Fidler IJ, Ellis LM. The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell 1994;79:185–188.

    Article  PubMed  CAS  Google Scholar 

  78. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1–7.

    Article  Google Scholar 

  79. Krah K, Mironov V, Risau W, Flamme I. Induction of vasculogenesis in quail blastodisc-derived embryoid bodies. Dev Biol 1994;164:123–132.

    Article  PubMed  CAS  Google Scholar 

  80. Shalaby F, et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature (Lond) 1995;6535(376):62–66.

    Article  Google Scholar 

  81. Ferrara N. Vascular endothelial growth factor and the regulation of angiogenesis. Recent Prog Horm Res 2000;55:15–35.

    PubMed  CAS  Google Scholar 

  82. Veikkola T, Karkkainen MJ, Claesson-Welsh L, Alitalo K. Regulation of angiogenesis via vascular endothelial growth factor receptors. Cancer Res 2000;60:203–212.

    PubMed  CAS  Google Scholar 

  83. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev 1997;18:4–25.

    Article  PubMed  CAS  Google Scholar 

  84. Bayless KJ, Salazar R, Davis GE. RGD-dependent vacuolation and lumen formation observed during endothelial cell morphogenesis in three-dimensional fibrin matrices involves the alpha(v)beta(3) and alpha(5)beta(1) integrins. Am J Pathol 2000;156:1673–1683.

    PubMed  CAS  Google Scholar 

  85. Thurston G, Rudge JS, Ioffe E. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 2000;6:1–4.

    Article  CAS  Google Scholar 

  86. Thurston G, et al. Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science 1999;286:2511–2514.

    Article  PubMed  CAS  Google Scholar 

  87. Suri C, Jones PF, Patan S. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 1996;87:1171–1180.

    Article  PubMed  CAS  Google Scholar 

  88. Maisonpierre PC, Suri C, Jones PF, et al. Angiopoietin-2, natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 1997;277:55–60.

    Article  PubMed  CAS  Google Scholar 

  89. Patan S, Munn LL, Jain RK. Intussusceptive microvascular growth in a human colon adenocarcinoma xenograft: a novel mechanism of tumor angiogenesis. Microvasc Res 1996;51:260–272.

    Article  PubMed  CAS  Google Scholar 

  90. Maniotis AJ, et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 1999;155:739–752.

    PubMed  CAS  Google Scholar 

  91. Folberg R, Hendrix MJ, Maniotis AJ. Vasculogenic mimicry and tumor angiogenesis. Am J Pathol 2000;156:361–381.

    PubMed  CAS  Google Scholar 

  92. Djonov V, Schmid M, Tschanz SA, Burri PH. Intussusceptive angiogenesis: its role in embryonic vascular network formation. Circ Res 2000;86:286–292.

    PubMed  CAS  Google Scholar 

  93. Rafii M. Circulating endothelial precursors: mystery, reality and promise. J Clin Invest 2000;105:17–19.

    Article  PubMed  CAS  Google Scholar 

  94. Asahara T, Kalka C, Isner JM. Stem cell therapy and gene transfer for regeneration. Gene Ther 2000;7:451–457.

    Article  PubMed  CAS  Google Scholar 

  95. Takahashi T, Kalka C, Masuda H. Ischemia-and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999;5:434–438.

    Article  PubMed  CAS  Google Scholar 

  96. Rafii S. Efficient mobilization and recruitment of marrow-derived endothelial and hematopoietic cells by adenoviral vectors expressing factors. Gene Ther 2002;9:631–641.

    Article  PubMed  CAS  Google Scholar 

  97. Lyden D, et al. Impaired recruitment of bone marrow-derived endothelial cells blocks tumour angiogenesis and growth. Nat Med 2001;7:1194–1201.

    Article  PubMed  CAS  Google Scholar 

  98. Asahara T, Takahashi T, Masuda H. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cell precursors. EMBO J 1999;18:3964–3972.

    Article  PubMed  CAS  Google Scholar 

  99. Kalka C, Masuda H, Takahashi T. Vascular endothelial growth factor (165) gene transfer augments circulating endothelial progenitor cells in human subjects. Circ Res 2000;86:1198–1202.

    PubMed  CAS  Google Scholar 

  100. Hattori K. Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J Exp Med 2001;193:1005–1014.

    Article  PubMed  CAS  Google Scholar 

  101. Reyes M, et al. Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest 2002;109:337–346.

    Article  PubMed  CAS  Google Scholar 

  102. Hattori K. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med 2002;8:841–849.

    PubMed  CAS  Google Scholar 

  103. Mandriota SJ, Pepper MS. Vascular endothelial growth factor-induced in vitro angiogenesis and plasminogen activator expression are dependent on endogenous basic fibroblast growth factor. J Cell Sci 1997;110:2293–2302.

    PubMed  CAS  Google Scholar 

  104. Lobov IB, Brooks PC, Lang RA. Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc Natl Acad Sci USA 2002;99:11205–11210.

    Article  PubMed  CAS  Google Scholar 

  105. McDonald DM, Munn LL, Jain RK. Vasculogenic mimicry: how convincing, how novel, and how significant. Am J Pathol 2000;156:383–388.

    PubMed  CAS  Google Scholar 

  106. Liotta LA, Steeg PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 1991;64:327–336.

    Article  PubMed  CAS  Google Scholar 

  107. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996;86:353–364.

    Article  PubMed  CAS  Google Scholar 

  108. Maxwell PH, Dachs GU, Gleadle JM. Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci USA 1997;94:8104–8109.

    Article  PubMed  CAS  Google Scholar 

  109. Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature (Lond) 1992;359:843–845.

    Article  PubMed  CAS  Google Scholar 

  110. Semenza GL. Surviving ischemia: adaptive responses mediated by hypoxia-inducible factor 1. J Clin Invest 2000;106:809–812.

    PubMed  CAS  Google Scholar 

  111. Semanza GL. Regulation of hypoxia-induced angiogenesis: a chaperone escorts VEGF to the dance. J Clin Invest 2001;108:39–40.

    Article  Google Scholar 

  112. Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 2002;20:4368–4380.

    Article  PubMed  CAS  Google Scholar 

  113. Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 2003;9:677–684.

    Article  PubMed  CAS  Google Scholar 

  114. Shweiki D, Neeman M, Itin A. Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: implications for tumor angiogenesis. Proc Natl Acad Sci USA 1995;92:768–772.

    Article  PubMed  CAS  Google Scholar 

  115. Banai S, et al. Upregulation of vascular endothelial growth factor expression induced by myocardial ischaemia: implications for coronary angiogenesis. Cardiovasc Res 1994;28:1176–1179.

    PubMed  CAS  Google Scholar 

  116. Bergers G, Brekken R, McMahon G. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2000;2:737–744.

    Article  PubMed  CAS  Google Scholar 

  117. Wang H, Keiser JA. Vascular endothelial growth factor upregulates the expression of matrix metalloproteinases in vascular smooth muscle cells: role of flt-1. Circ Res 1998;83:832–840.

    PubMed  CAS  Google Scholar 

  118. Arbiser JL, Moses MA, Fernandez CA. Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways. Proc Natl Acad Sci USA 1997;94: 861–866.

    Article  PubMed  CAS  Google Scholar 

  119. Laughner E, Taghavi P, Chiles K. HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1 alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Mol Cell Biol 2001;21:3995–4004.

    Article  PubMed  CAS  Google Scholar 

  120. Ravi R, Mookerjee B, Bhujwalla ZW. Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev 2000;14:34–44.

    PubMed  CAS  Google Scholar 

  121. Bergsmedh A, et al. Horizontal transfer of oncogenes by uptake of apoptotic bodies. Proc Natl Acad Sci USA 2001;98:6407–6411.

    Article  PubMed  CAS  Google Scholar 

  122. Rosen L. Antiangiogenic strategies and agents in clinical trials. Oncologist 2000;5:20–27.

    Article  PubMed  CAS  Google Scholar 

  123. Stacker SA, Achen MG, Jussila L, Baldwin ME, Alitalo K. Lymphangiogenesis and cancer metastasis. Nat Rev Cancer 2002;2:573–583.

    Article  PubMed  CAS  Google Scholar 

  124. Jussila L, Alitalo K. Vascular growth factors and lymphangiogenesis. Physiol Rev 2002;82:673–700.

    PubMed  CAS  Google Scholar 

  125. Karkkainen MJ, Makinen T, Alitalo K. Lymphatic endothelium: a new frontier of metastasis research. Nat Cell Biol 2002;4:E2–E5.

    Article  PubMed  CAS  Google Scholar 

  126. Fisher B, et al. relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update. Cancer (Phila) 1983;52:1551–1557.

    Article  PubMed  CAS  Google Scholar 

  127. Hein DW, Moy RL. Elective lymph node dissection in stage I malignant melanomas: a meta-analysis. Melanoma Res 1992;2:273.

    Article  PubMed  CAS  Google Scholar 

  128. Enker E, Laffer UT, Block GE. Enhanced survival of patients with colon and rectal cancer is based upon wide anatomic resection. Ann Surg 1979;190:350.

    Article  PubMed  CAS  Google Scholar 

  129. Beasley NJ, et al. Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer. Cancer Res 2002;62:1315–1320.

    PubMed  CAS  Google Scholar 

  130. Pepper MS. Lymphangiogenesis and tumor metastasis: myth or reality. Clin Cancer Res 2001;7:462–468.

    PubMed  CAS  Google Scholar 

  131. Leu AJ, Berk DA, Lymboussaki A, Alitalo K, Jain RK. Absence of functional lymphatics within a murine sarcoma: a molecular and functional evaluation. Cancer Res 2000;60:4324–4327.

    PubMed  CAS  Google Scholar 

  132. Stacker SA, Baldwin ME, Achen MG. The role of tumor lymphangiogenesis in metastatic spread. FASEB J 2002;16:922–934.

    Article  PubMed  CAS  Google Scholar 

  133. Padera TP, et al. Lymphatic metastasis in the absence of functional intratumor lymphatics. Science 2002;296:1883–1886.

    Article  PubMed  CAS  Google Scholar 

  134. Jain RK, Fenton BT. Intratumoral lymphatic vessels: a case of mistaken identity or malfunction? J Natl Cancer Inst 2002;94:417–421.

    PubMed  Google Scholar 

  135. Oh S, et al. VEGF and VEGF-C specific induction of angiogenesis and lymphangiogenesis in the differentiated avian chorioallantoic membrane. Dev Biol 1997;188:96–109.

    Article  PubMed  CAS  Google Scholar 

  136. Jeltsch M, et al. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science 1997;276:1423–1425.

    Article  PubMed  CAS  Google Scholar 

  137. Skobe M, et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med 2001;7:192–198.

    Article  PubMed  CAS  Google Scholar 

  138. Achen MG, et al. Vascular endothelial growth factor D (Vegf-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk-1) and VEGF receptor 3 (Flt-4). Proc Natl Acad Sci USA 1998;95:548–553.

    Article  PubMed  CAS  Google Scholar 

  139. Stacker SA, et al. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med 2001;7:186–191.

    Article  PubMed  CAS  Google Scholar 

  140. Veikkola T, et al. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. EMBO J 2001;20:1223–1231.

    Article  PubMed  CAS  Google Scholar 

  141. Kukk E, et al. VEGF-C receptor binding and pattern of expression with VEGFR-3 receptor binding suggests role in lymphatic vascular development. Development (Camb) 1996;122:3829–3837.

    PubMed  CAS  Google Scholar 

  142. Cassella M, Skobe M. Lymphatic vessel activation in cancer. Ann NY Acad Sci 2002;979:120–130.

    PubMed  CAS  Google Scholar 

  143. Mandriota SJ, et al. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J 2001;20:672–682.

    Article  PubMed  CAS  Google Scholar 

  144. Woodhouse EC, Chuaqui RF, Liotta LA. General mechanisms of metastasis. Cancer (Phila) 1997;80:1529–1537.

    Article  PubMed  CAS  Google Scholar 

  145. Comoglio PM, Trusolino L. Invasive growth: from development to metastasis. J Clin Invest 2992;109:857–862.

    Google Scholar 

  146. Stossel TP. On the crawling of animal cells. Science 1993;260: 1086–1094.

    Article  PubMed  CAS  Google Scholar 

  147. El-Badry OM, et al. Insulin-like growth factor II acts as an autocrine growth and motility factor in human rhabdomyosarcoma tumors. Cell Growth Differ 1990;1325–351.

    Google Scholar 

  148. Stracke ML, et al. Identification, purification and partial sequence analysis of autoaxin, a novel motility-stimulating protein. J Biol Chem 1992;267:2524–2529.

    PubMed  CAS  Google Scholar 

  149. Stracke ML, et al. Insulin-like growth factors stimulate chemotaxis in human melanoma cells. Biochem Biophys Res Commun 1988;153:1076–1083.

    Article  PubMed  CAS  Google Scholar 

  150. McCarthy JB, Furcht LT. Laminin and fibronectin promote the haptotoactic migration of B16 mouse melanoma cells in vitro. J Cell Biol 1984;98:1474–1480.

    Article  PubMed  CAS  Google Scholar 

  151. Tchao R. Novel forms of epithelial cell motility on collagen and on glass surfaces. Cell Motil 1982;2:333–341.

    Article  PubMed  CAS  Google Scholar 

  152. Ray JM, Stetler-Stevenson WG. The role of matrix metalloproteases and their inhibitors in tumor invasion, metastasis, and angiogenesis. Eur Respir J 1994;7:2062–2072.

    PubMed  CAS  Google Scholar 

  153. Sledge GW Jr, Miller KD. Exploiting the hallmarks of cancer: the future conquest of breast cancer. Eur J Cancer 2003;39:1668–1675.

    Article  PubMed  Google Scholar 

  154. Morikawa K, et al. Influence of organ microenvironment on extracellular matrix degradative activity and metastasis of human colon carcinoma cells. Cancer Res 1988;48:6863–6871.

    PubMed  CAS  Google Scholar 

  155. Stetler-Stevenson M. Type IV collagenase in tumor invasion and metastases. Cancer Metastasis Rev 1990;9:289–303.

    Article  PubMed  CAS  Google Scholar 

  156. Weidner N. New paradigm for vessel intravasation by tumor cells. Am J Pathol 2002;160:1937–1939.

    PubMed  Google Scholar 

  157. Dvorak HF, et al. Vascular permeability factor/vascular endothelial growth factor: an important mediator of angiogenesis in malignancy and inflammation. Int Arch Allergy Immunol 1955;107:233–235.

    Article  Google Scholar 

  158. Dvorak HF, et al. Distribution of vascular permeability factor (vascular endothelial growth factor) in tumors: concentration in tumor blood vessels. J Exp Med 1991;174:1275–1278.

    Article  PubMed  CAS  Google Scholar 

  159. Poste G, Fidler IJ. The pathogenesis of cancer metastasis. Nature (Lond) 1980;283:139–146.

    Article  PubMed  CAS  Google Scholar 

  160. Lee Y. Breast carcinoma: pattern of metastasis at autopsy. J Surg Oncol 1983;23:175–180.

    Article  PubMed  CAS  Google Scholar 

  161. Welch JP, Donaldson GA. The clinical correlation of an autopsy study of recurrent colorectal cancer. Ann Surg 1979;189:496–502.

    Article  PubMed  CAS  Google Scholar 

  162. Lee Y. Malignant melanoma: patterns of metastasis. CA Cancer J Clin 1980;30:137.

    PubMed  CAS  Google Scholar 

  163. Paget S. The distribution of secondary growths in cancer of the breast. Cancer Metastasis Rev 1989;8:98–101.

    PubMed  CAS  Google Scholar 

  164. Ewing J. Neoplastic Diseases. Philadelphia: Saunders, 1928:77–89.

    Google Scholar 

  165. Weiss L, et al. Haematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necropsies. J Pathol 1986;150:195–203.

    Article  PubMed  CAS  Google Scholar 

  166. Tarin D, et al. Mechanism of human tumor metastasis studied in patients with peritoneovenous shunts. Cancer Res 1984;44:3584–3592.

    PubMed  CAS  Google Scholar 

  167. Tarin D, Vass ACR, Kettlewell MGW, Price JE. Absence of metastatic sequelae during long-term treatment of malignant ascites by perito-venous shunting. Invasion Metastasis 1984;4:1–12.

    PubMed  CAS  Google Scholar 

  168. Hart IR, Fidler IJ. Role of organ selectivity in the determination of metastatic patterns of B16 melanoma. Cancer Res 190;40:2281–2287.

    Google Scholar 

  169. Biancone L, Araki M, Araki K, Vassalli P, Stamenkovic I. Redirection of tumor metastasis by expression of E-selectin in vivo. J Exp Med 1996;183:581–587.

    Article  PubMed  CAS  Google Scholar 

  170. Matsura N, et al. Induction of experimental bone metastasis in mice by transfection of integrin alpha 4 beta 1 into tumor cells. Am J Pathol 1996;148:55–61.

    Google Scholar 

  171. Auerbach R, Alby L, Morrissey LW, Tu M, Joseph J. Expression of organospecific antigens on capillary endothelial cells. Microvasc Res 1985;29:401–411.

    Article  PubMed  CAS  Google Scholar 

  172. Rajotte D, et al. Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display. J Clin Invest 1998;102:430–437.

    Article  PubMed  CAS  Google Scholar 

  173. Auerbach R, et al. Specificity of adhesion between murine tumor cells and capillary endothelium: an in vitro correlate of preferential metastasis in vivo. Cancer Res 1987;47:1492–1496.

    PubMed  CAS  Google Scholar 

  174. Ruoslahti E, Rajotte D. An address system in the vasculature of normal tissues and tumors. Annu Rev Immunol 2000;18:813–827.

    Article  PubMed  CAS  Google Scholar 

  175. Pasqualini R, Ruoslahti E. Organ targeting in vivo using phage display peptide libraries. Nature (Lond) 1996;380:364–366.

    Article  PubMed  CAS  Google Scholar 

  176. Arap W, et al. Steps towards mapping the human vasculature by phage display. Nat Med 2002;8:121–127.

    Article  PubMed  CAS  Google Scholar 

  177. Johnson RC, Zhu DX, Augustin-Voss HG, Pauli BU. Lung endothelial dipeptidyl peptidase IV is an adhesion molecule for lung-metastatic rat breast and prostate carcinoma cells. J Cell Biol 1993;121:1423–1432.

    Article  PubMed  CAS  Google Scholar 

  178. Rajotte D, Ruoslahti E. Membrane dipeptidase is the receptor for a lung-targeting peptide indentified by in vivo phage display. J Biol Chem 1999;274(17):11593–11598.

    Article  PubMed  CAS  Google Scholar 

  179. Essler M, Ruoslahti E. Molecular specialization of breast vasculature: a breast-homing phage-displayed peptide binds to aminopeptidase P in breast vasculature. Proc Natl Acad Sci USA 2002;99:2252–2257.

    Article  PubMed  CAS  Google Scholar 

  180. Ngaiza JR, Walter S, Barghava P, Malerczyk C, Wellstein A. Pa28alpha: a liver homing protein identified from a colon cancer cell line by in vivo phage display. In: AACR Meeting, New Orleans, 2001;42:261 (abstract).

    Google Scholar 

  181. Koop S, et al. Independence of metastatic ability and extravasation: metastatic ras-transformed and control fibroblasts extravasate equally well. Proc Natl Acad Sci USA 1996;93:11080–11084.

    Article  PubMed  CAS  Google Scholar 

  182. Morris VL, Schmidt EE, MacDonald IC, Groom AC, Chambers AF. Sequential steps in hematogenous metastasis of cancer cells studied by in vivo videomicroscopy. Invasion Metastasis 1997;17:281–296.

    PubMed  CAS  Google Scholar 

  183. Groom AC, MacDonald IC, Schmidt EE, Morris VL, Chambers AF. Tumor metastasis to the liver, the roles of proteinases and adhesion molecules: new concepts from in vivo videomicroscopy. Can J Gastroenterol 1999;13:733–743.

    PubMed  CAS  Google Scholar 

  184. Heyder C, et al. Real time visualization of tumor cell/endothelial cell interactions during transmigration across the endothelial barrier. J Cancer Res Clin Oncol 2002;128:533–538.

    Article  PubMed  CAS  Google Scholar 

  185. Siegel PM, Shu W, Cardiff RD, Muller WJ, Massague J. Transforming growth factor beta signaling impairs neu-induced mammary tumorigenesis while promoting pulmonary metastasis. Proc Natl Acad Sci USA 2003;100:8430–8435.

    Article  PubMed  CAS  Google Scholar 

  186. Laferriere J, Houle F, Huot J. Regulation of the metastatic process by E-selectin and stress-activated protein kinase-2/p38. Ann NY Acad Sci 2002;973:562–572.

    PubMed  CAS  Google Scholar 

  187. Roetger A, et al. Selection of potentially metastatic subpopulations expressing c-erbB-2 from breast cancer tissue by use of an extravasation model. Am J Pathol 1998;153:1797–1806.

    PubMed  CAS  Google Scholar 

  188. Satoh H, et al. Localization of 7H6 tight junction-associated antigen along the cell border of vascular endothelial cells correlates with paracellular barrier function against ions, large molecules and cancer cells. Exp Cell Res 1996;222:269–274.

    Article  PubMed  CAS  Google Scholar 

  189. Tobioka H, Sawada N, Zhong Y, Mori M. Enhanced paracellular barrier function of rat mesothelial cells partially protects against cancer cell penetration. Br J Cancer 1996;74:439–445.

    PubMed  CAS  Google Scholar 

  190. Osani M, et al. Hepatocyte nuclear factor (HNF)-4alpha induces expression of endothelial fas ligand (fasl) to prevent cancer cell migration: a novel defense mechanism of endothelium against cancer metastasis. Jpn J Cancer Res 2002;93:532–541.

    Google Scholar 

  191. Lewalle JM, Cataldo D, Bajou K, Lambert CA, Foidart JM. Endothelial cell intracellular Ca2+ concentration is increased upon breast tumor cell contact and mediates tumor cell transendothelial migration. Clin Exp Metastasis 1998;16:21–29.

    Article  PubMed  CAS  Google Scholar 

  192. Voura EB, Sandig M, Kalnins VI, Siu C. Cell shape changes and cytoskeletal reorganization during transendothelial migration of human melanoma cells. Cell Tissue Res 1998;293:375–387.

    Article  PubMed  CAS  Google Scholar 

  193. Madri JA, Graesser D. Cell migration in the immune system: the evolving inter-related roles of adhesion molecules and proteinases. Dev Immunol 2000;7:103–116.

    PubMed  CAS  Google Scholar 

  194. Faveeuw C, Preece G, Ager A. Transendothelial migration of lymphocytes across high endothelial venules into lymph nodes is affected by metalloproteinases. Immunobiology 2001;98:688–695.

    CAS  Google Scholar 

  195. Leppert D, et al. Stimulation of matrix metalloproteinase-dependent migration of T cells by eicosanoids. FASEB J 1995;9:1473–1481.

    PubMed  CAS  Google Scholar 

  196. Leppert D, Waunbant E, Galardy R, Bunnett N, Hauser SL. T-cell gelatinases mediate basement membrane transmigration in vitro. J Immunol 1995;154:4379–4389.

    PubMed  CAS  Google Scholar 

  197. Madri JA, Graesser D, Haas T. The roles of adhesion molecules and proteinases in lymphocyte transendothelial migration. Biochem Cell Biol 1996;74:749–757.

    Article  PubMed  CAS  Google Scholar 

  198. Klier CM, Nelson PJ. Chemokine-induced extravasation of MonoMac 6 cells: chemotaxis and MMP activity. Ann NY Acad Sci 1999;878:575–577.

    Article  PubMed  CAS  Google Scholar 

  199. Robinson SC, Scott KA, Balkwill FR. Chemokine stimulation of monocyte matrix metalloproteinase-9 requires endogenous TNF-alpha. Eur J Immunol 2002;32:404–412.

    Article  PubMed  CAS  Google Scholar 

  200. Yoon SO, Park SJ, Yun CH, Chung AS. Roles of matrix metalloproteinases in tumor metastasis and angiogenesis. J Biochem Mol Biol 2003;36:128–137.

    PubMed  CAS  Google Scholar 

  201. Kuittinen O, Savolainen E, Koisten P, Mottonen M, Turpeenniemi-Hujanen T. MMP-2 and MMP-9 expression in adult and childhood acute lymphatic leukemia (ALL). Leukemia Res 2001;25:125–132.

    Article  CAS  Google Scholar 

  202. Roberts AB, Wakefield LM. The two faces of transforming growth factor beta in carcinogenesis. Proc Natl Acad Sci USA 2003;15:8621–8623.

    Article  CAS  Google Scholar 

  203. Stamenkovic I. Matrix metalloproteinases in tumor invasion and metastasis. Cancer Biol 2000;10:415–433.

    Article  CAS  Google Scholar 

  204. Cairns RA, Khokha R, Hill RP. Molecular mechanisms of tumor invasion and metastasis: an integrated view. Curr Mol Med 2003;3:659–671.

    Article  PubMed  CAS  Google Scholar 

  205. Fidler IJ. Seed and soil revisited: contribution of the organ microenvironment to cancer metastasis. Surg Oncol Clin N Am 2001;10:257–269.

    PubMed  CAS  Google Scholar 

  206. Berman RS, Portera CA, Ellis LM. Biology of liver metastases. Cancer Treat Res 2001;209:183–206.

    Google Scholar 

  207. Bashyam MD. Understanding cancer metastasis. Cancer (Phila) 2002;94:1821–1829.

    Article  PubMed  CAS  Google Scholar 

  208. Duncan LM, Deeds J, Hunter J. Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis. Cancer Res 1998;58:1515–1520.

    PubMed  CAS  Google Scholar 

  209. Ince TA, Weinberg RA. Functional genomics and the breast cancer problem. Cancer Cell 2002;1:15–17.

    Article  PubMed  CAS  Google Scholar 

  210. van’t Veer LJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature (Lond) 2002;415:530–536.

    Article  Google Scholar 

  211. Ramaswamy S, Ross KN, Lander ES, Golub TR. A molecular signature of metastasis in primary solid tumors. Nat Genet 2003;33:49–54.

    Article  PubMed  CAS  Google Scholar 

  212. Ngaiza JR, Walter S, Barghava P, Malerczyk C, Wellstein A. Pa28alpha: a liver homing protein identified from a colon cancer cell line by in vivo phage display. In: AACR Meeting, New Orleans, 2001;42:261 (abstract 1411).

    Google Scholar 

  213. Yu D, Hung M. Overexpression of ErbB2 in cancer and ErbB2-targeting strategies. Oncogene 2000;19:6115–6121.

    Article  PubMed  CAS  Google Scholar 

  214. Rowinsky EK. Signal events: cell signal transduction and its inhibition in cancer. Oncologist 2003;8:5–17.

    Article  PubMed  CAS  Google Scholar 

  215. Ciardielli F, Tortora G. A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res 2001;7:2958–2970.

    Google Scholar 

  216. Thompson TC, Timme TL, Goltsov A. Caveolin-1, a metastasis-related gene that promotes cell survival in prostate cancer. Apoptosis 1999;4:233–237.

    Article  PubMed  CAS  Google Scholar 

  217. Kraiem Z, Korem S. Matrix metalloproteinases and the thyroid. Thyroid 2000;10:1061–1069.

    PubMed  CAS  Google Scholar 

  218. Elkin M, et al. Inhibition of matrix metalloproteinase-2 expression and bladder carcinoma metastasis by halofuginone. Clin Cancer Res 1999;5:1982–1988.

    PubMed  CAS  Google Scholar 

  219. Tremont-Lukats IW, Gilbert MR. Advances in molecular therapies in patients with brain tumors. Cancer Control 2003;10:125–137.

    PubMed  Google Scholar 

  220. Ouatas M, Salerno M, Palmieri T, Steeg PS. Basic and translational advances in cancer metastasis: Nm23. J Bioenerg Biomembr 2003;35:73–79.

    Article  PubMed  CAS  Google Scholar 

  221. Welsh SJ, Powis G. Hypoxia inducible factor as a cancer drug target. Curr Cancer Drug Targets 2003;3:391–405.

    Article  PubMed  CAS  Google Scholar 

  222. Chambers AF, MacDonald IC, Schmidt EE, Morris VL, Groom AC. Clinical targets for anti-metastasis therapy. Adv Cancer Res 2000;79:91–121.

    PubMed  CAS  Google Scholar 

  223. Kim JA. Targeted therapies for the treatment of cancer. Am J Surg 2003;186:264–268.

    Article  PubMed  CAS  Google Scholar 

  224. Niethammer AG, et al. A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth. Nat Med 2002;8:1369–1375.

    Article  PubMed  CAS  Google Scholar 

  225. Willett CG, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 2003;10:145–147.

    Article  CAS  Google Scholar 

  226. Arap W, et al. Targeting the prostate for destruction through a vascular address. Proc Natl Acad Sci USA 2002;99:1527–1531.

    Article  PubMed  CAS  Google Scholar 

  227. Ruoslahti E. Targeting tumor vasculature with homing peptides from phage display. Cancer Biol 2000;10:435–442.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Lombardi Cancer Center, Georgetown University, Washington, DC, USA

    Kevin McDonnell MD, PhD (Fellow) & Anton Wellstein MD, PhD (Professor)

Authors
  1. Kevin McDonnell MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anton Wellstein MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Surgery Oncology, Department of Surgery, University of Michigan, Ann Arbor, MI, USA

    Alfred E. Chang MD (Hugh Cabot Professor of Surgery and Chief) (Hugh Cabot Professor of Surgery and Chief)

  2. Breast Oncology Program, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA

    Daniel F. Hayes MD (Clinical Director) (Clinical Director)

  3. Department of Cardiothoracic Surgery, New York University School of Medicine and Comprehensive Cancer Center, New York, NY, USA

    Harvey I. Pass MD (Professor and Chief of Thoracic Surgery and Head) (Professor and Chief of Thoracic Surgery and Head)

  4. Thoracic Oncology, New York University School of Medicine and Comprehensive Cancer Center, New York, NY, USA

    Harvey I. Pass MD (Professor and Chief of Thoracic Surgery and Head) (Professor and Chief of Thoracic Surgery and Head)

  5. Department of Medicine, Harvard Medical School, USA

    Richard M. Stone MD (Associate Professor and Clinical Director) (Associate Professor and Clinical Director)

  6. Adult Leukemia Program, Dana-Farber Cancer Institute, Boston, MA, USA

    Richard M. Stone MD (Associate Professor and Clinical Director) (Associate Professor and Clinical Director)

  7. Division of Cancer Prevention and Control Research, Jonsson Comprehensive Cancer Center at UCLA, USA

    Patricia A. Ganz MD (American Cancer Society Clinical Research Professor, Director and Professor) (American Cancer Society Clinical Research Professor, Director and Professor)

  8. Schools of Public Health and Medicine, University of California, Los Angeles, Los Angeles, CA, USA

    Patricia A. Ganz MD (American Cancer Society Clinical Research Professor, Director and Professor) (American Cancer Society Clinical Research Professor, Director and Professor)

  9. Department of Radiation Oncology, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH, USA

    Timothy J. Kinsella MD (Vincent K. Smith Professor and Chairman) (Vincent K. Smith Professor and Chairman)

  10. Department of Medicine, University of Wisconsin Comprehensive Cancer Center, Madison, WI, USA

    Joan H. Schiller MD (Melanie Heald Professor of Medical Oncology) (Melanie Heald Professor of Medical Oncology)

  11. Health Media Research Laboratory, Department of Health Behavior and Health Education, University of Michigan School of Public Health, USA

    Victor J. Strecher PhD, MPH (Professor and Director and Associate Director) (Professor and Director and Associate Director)

  12. Cancer Prevention and Control, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA

    Victor J. Strecher PhD, MPH (Professor and Director and Associate Director) (Professor and Director and Associate Director)

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer Science+Business Media, Inc.

About this chapter

Cite this chapter

McDonnell, K., Wellstein, A. (2006). Cancer Metastasis. In: Chang, A.E., et al. Oncology. Springer, New York, NY. https://doi.org/10.1007/0-387-31056-8_19

Download citation

  • DOI: https://doi.org/10.1007/0-387-31056-8_19

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-0-387-24291-0

  • Online ISBN: 978-0-387-31056-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation