Tumor Angiogenesis: Importance in Tumor Detection and Growth

  • Gerald W. Chodak
  • Judah Folkman
Part of the Cancer Treatment and Research book series (CTAR, volume 19)


Tumor angiogenesis has been defined as the growth of new capillary blood vessels in response to a tumor stimulus. This process is caused by a diffusable tumor product(s) and is directly responsible for enabling tumors to enlarge in size. Over the last ten years, significant progress has been made toward understanding the mechanism of this response. In addition, there now appears to be a potential for exploiting this understanding in order to assist with the diagnosis and possibly the treatment of solid tumors. This chapter will present an overview of the current knowledge in this field and the potential direction for this area in the near future.


Capillary Endothelial Cell Angiogenic Activity Protamine Sulfate Rabbit Cornea Capillary Growth 
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  1. 1.
    Algire GH, Chalkley HW, Legallais FY, Park HD: Vascular reactions of normal and malignant tissues in vivo. I. Vascular reactions of mice to wounds and to normal and neoplastic transplants. J Natl Cancer Inst 6:73, 1945.Google Scholar
  2. 2.
    Ausprunk DH, Folkman J: Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Micro vas Res 14:53, 1977.CrossRefGoogle Scholar
  3. 3.
    Azizkhan RG, Azizkhan JC, Zetter BR, Folkman J: Mast cell heparin stimulates migration of capillary endothelial cells in vitro. J Exp Med 152:931, 1980.PubMedCrossRefGoogle Scholar
  4. 4.
    Ben Ezra D: Neovasculogenic ability of prostaglandins, growth factors, and synthetic chemoattractants. Am J Ophthalmol. 86:455, 1978.Google Scholar
  5. 5.
    Brem S, Brem H, Folkman J, Finkelstein, Patz A: Prolonged tumor dormancy by prevention of neovascularization in the vitreous. Can Res 36:2807, 1976.Google Scholar
  6. 6.
    Brem H, Folkman J: Inhibition of tumor angiogenesis mediated by cartilage. J Exp Med 141:427, 1975.PubMedCrossRefGoogle Scholar
  7. 7.
    Brem SS, Gullino PM, Medina D: Angiogenesis: a marker for neoplastic transformation of mammary papillary hyperplasia. Science 199:880, 1977.CrossRefGoogle Scholar
  8. 8.
    Bremm SS, Jensen HM, Gullino PM: Angiogenesis as a marker of preneoplastic lesions of the human breast. Cancer 41:239, 1978.CrossRefGoogle Scholar
  9. 9.
    Chodak GW, Haudenschild C, Gittes RF, Folkman J: Angiogenic activity as a marker of neoplastic and preneoplastic lesions of the human bladder. Ann Surg 192:762, 1980.PubMedCrossRefGoogle Scholar
  10. 10.
    Chodak GW, Scheiner CJ, Zetter BR: Urine from patiens with transitional-cell carcinoma stimulates migration of capillary endothelial cells. New Engl J Med 305:869, 1981.PubMedCrossRefGoogle Scholar
  11. 11.
    Chodak GW, Summerhays L, Folkman J: Angiogenesis assay of benign and malignant mammalian urothelium. Surg Forum 31:587, 1980.Google Scholar
  12. 12.
    Eisenstein R, Kuettner KE, Neapolitan C, Soble LW, Sorgente N: The resistance of certain tissues to invasion. III. Cartilage extracts inhibit the growth of fibroblasts and endothelial cells in culture. Am J Pathol 81:337, 1975.PubMedGoogle Scholar
  13. 13.
    Eisenstein R, Sorgente N, Soble LW, Miller A, Kuettner KE: The resistance of certain tissues to invasion. Penetrability of explanted tissues by vascularized mesenchyme. Am J Pathol 73:765, 1973.PubMedGoogle Scholar
  14. 14.
    Falterman KW, Ausprunk DH, Klein MD: Role of tumor angiogenesis factor in maintenance of tumor-induced vessels. Surg Forum 27:157, 1976.PubMedGoogle Scholar
  15. 15.
    Folkman J, Cotran R: Relation of vascular proliferation to tumor growth. Int Rev Exp Pathol 16:207, 1976.PubMedGoogle Scholar
  16. 16.
    Folkman J, Hochberg M: Self-regulation of growth in three dimensions. J Exp Med 138:745, 1973.PubMedCrossRefGoogle Scholar
  17. 17.
    Form DM, Sidky YA, Kubai L, Auerbach R: PGE2-induced angiogenesis. Prostaglandins and cancer: In: First International Conference. New York: Alan R. Liss Inc, p 685, 1982.Google Scholar
  18. 18.
    Gimbrone MA, Jr, Gullino P: Neovascularization induced by intraocular xenografts of normal, preneoplastic and neoplastic mouse mammary tissues. J Natl Cancer Inst 56:305, 1976.PubMedGoogle Scholar
  19. 19.
    Gimbrone MA, Jr, Leapman SB, Cotran RS et al: Tumor dormancy in vivo by prevention of neovascularization. J Exp Med 136:261, 1072.CrossRefGoogle Scholar
  20. 20.
    Greenblatt M, Shubik P: Tumor angiogenesis: transfilter diffusion studies in the hamster by the transparent chamber technique. J Natl Cancer Inst 41:111, 1968.PubMedGoogle Scholar
  21. 21.
    Kelly PJ, Suddith RL, Hutchison HT et al: Endothelial growth factor present in tissue culture of CNS tumors. J Neurosurg 44:342, 1976.PubMedCrossRefGoogle Scholar
  22. 22.
    Kessler DA, Langer RS, Pless NA, Folkman J: Mast cells and tumor angiogenesis. Int J Cancer 18:703, 1976.PubMedCrossRefGoogle Scholar
  23. 23.
    Klagsbrun M, Knighton D, Folkman J: Tumor angiogenesis activity in cells grown in tissue culture. Cancer Res 36:110, 1976.PubMedGoogle Scholar
  24. 24.
    Knighton D, Ausprunk D, Tapper D, Folkman J: Avascular and vascular phases of tumour growth in the chick embryo. Br J Cancer 35:347, 1977.PubMedCrossRefGoogle Scholar
  25. 25.
    Langer R, Brem H, Falterman K et al: Isolation of a cartilage factor that inhibits tumor neovascularization. Science 193:70, 1976.PubMedCrossRefGoogle Scholar
  26. 26.
    Langer R, Conn H, Vacanti J et al: Control of tumor growth in animals by infusion of an angiogenesis inhibitor. Proc Natl Acad Sci USA 77:4331, 1980.PubMedCrossRefGoogle Scholar
  27. 27.
    Lopez-Pousa S, Ferner L, Vich JM, Domenech-Mateu J: Angiogenic activity in CSF in human malignancies. Experientia 37:413, 1981.PubMedCrossRefGoogle Scholar
  28. 28.
    Matsuno H: Tumor angiogenesis factor (TAF) in cultured cells derived from central nervous system tumors in humans. Neurol Med Chir (Tokyo) 21:765, 1981.CrossRefGoogle Scholar
  29. 29.
    McAuslan BR: A new theory of neovascularisation based on identification of an angiogenic factor and its effect on cultured endothelial cells. In: Control Mechanisms in Animal Cells, Jimenez de Asua et al. L. (eds.) New York: Raven Press, p 285, 1980.Google Scholar
  30. 30.
    McAuslan BR, Reily W: Endothelial cell phagokinesis in response to specific metal ions. Exp Cell Res 130:147, 1980.PubMedCrossRefGoogle Scholar
  31. 31.
    Phillips P, Kumar S: Tumour angiogenesis factor (TAF) and its neutralisation by a xenogeneic antiserum. Int J Cancer 23:82, 1979.PubMedCrossRefGoogle Scholar
  32. 32.
    Sakamoto S, Goldhaber P, Glimcher MJ: Mouse bone collagenase: the effect of heparin on the amount of enzyme released in tissue culture and on the activity of the enzyme. Calif Tissue Res 12:247, 1973.CrossRefGoogle Scholar
  33. 33.
    Sorgante N, Kuettner KE, Soble LW, Eisenstein R: The resistance of certain tissues to invasion. II. Evidence for extractable factors in cartilage which inhibit invasion by vascularized mesenchyme. Lab Invest 32:217, 1975.Google Scholar
  34. 34.
    Suddith RL, Kelly PJ, Hutchison HT et al: In vitro demonstration of endothelial proliferative factor produced by neural cell lines. Science 190:682, 1975.PubMedCrossRefGoogle Scholar
  35. 35.
    Tapper D, Langer R, Bellows AR, Folkman J: Angiogenesis capacity as a diagnostic marker for human eye tumors. Surgery 86:36, 1979.PubMedGoogle Scholar
  36. 36.
    Taylor S, Folkman J: Protamine is an inhibitor of angiogenesis. Nature 297:27, 1982.CrossRefGoogle Scholar
  37. 37.
    Zetter BR: Migration of capillary endothelial cells is stimulated by tumour derived factors. Nature 285:41, 1980.PubMedCrossRefGoogle Scholar
  38. 38.
    Ziehe M, Gullino PM: Angiogenesis and neoplastic progression in vitro. J Natl Cancer Inst 69:483, 1982.Google Scholar
  39. 39.
    Ziehe M, Jones J, Gullino P: Role of prostaglandin El and copper in angiogenesis. J Natl Cancer Inst 69:475, 1982.Google Scholar
  40. 1.
    Algire GJ: J Natl Cancer Inst 4:13–20, 1943.Google Scholar
  41. 2.
    Greenblatt M, Shubik P: J Natl Cancer Inst 41:111–124, 1968.PubMedGoogle Scholar
  42. 3.
    Folkman J: In: Carcinoma of the Colon and Antecedent Epithelium, Burdette WJ (ed). Springfield: C.C. Thomas, pp 113–127, 1970.Google Scholar
  43. 4.
    Folkman J: In: Advances in Cancer Research, Klein G, Weinhouse S (eds). New York: Academic Press, 331–358, 1947.Google Scholar
  44. 5.
    Folkman J, Cotran RS: In: International Review of Experimental Pathology, Richter GW, (ed). New York: Academic Press, pp 207–248, 1976.Google Scholar
  45. 6.
    Folkman J: Ann Surg 175:409–416, 1972.PubMedCrossRefGoogle Scholar
  46. 7.
    Gimbrone MA Jr, Leapman S, Cotran RS, Folkman J: JNCI. 52:413–427, 1974.PubMedGoogle Scholar
  47. 8.
    Klagsbrun M, Knighton D, Folkman J: Cancer Res 36:110–114, 1976.PubMedGoogle Scholar
  48. 9.
    Langer R, Folkman J: Nature 263:797–800, 1976.PubMedCrossRefGoogle Scholar
  49. 10.
    Folkman J, Haudenschild CC, Zetter B: Proc Natl Acad Sci USA 76:5217–5221, 1979.PubMedCrossRefGoogle Scholar
  50. 11.
    Auerbach R: Lymphokines 4:69–88, 1981.Google Scholar
  51. 12.
    Polverini PJ, Cotran RS, Gimbrone MJ Jr, Unanue ER: Nature 269:804–806, 1977.PubMedCrossRefGoogle Scholar
  52. 13.
    Banda MJ, Knighton DR, Hunt TK, Werb Z: Proc Natl Acad Sci USA 79:7773–7777, 1982.PubMedCrossRefGoogle Scholar
  53. 14.
    Knighton DR, Hunt TK, Scheuenstuht H. Halliday H: Science 221:1283–1285, 1983.PubMedCrossRefGoogle Scholar
  54. 15.
    Eisenstein R, Sorgente N, Soble LW, Miller A, Kuettner KE: AM J Pathol 73:765–774, 1973.PubMedGoogle Scholar
  55. 16.
    Eisenstein R, Kuettner K, Neapolitan C, Soble LW, Sorgente N: Am J Pathol 81:337–347, 1975.PubMedGoogle Scholar
  56. 17.
    Brem H, Folkman J: J Exp Med 141:427–439, 1975.PubMedCrossRefGoogle Scholar
  57. 18.
    Brem SS, Jensen HM, Gullino PM: Cancer 41:239–244, 1978.PubMedCrossRefGoogle Scholar
  58. 19.
    Ziche M, Gullino PM: J Natl Cancer Inst 69:483–487, 1982.PubMedGoogle Scholar
  59. 20.
    Chodak GW, Scheiner CJ, Zetter BR: New Engl J Med 305:869–874, 1971.CrossRefGoogle Scholar
  60. 21.
    Zetter BR: Nature 285:41–43, 1981.CrossRefGoogle Scholar
  61. 22.
    Schor AM, Kumar S, Phillips PJ: Int J Cancer 25:773, 1980.PubMedCrossRefGoogle Scholar
  62. 23.
    Fenselau A, Watt S, Mello RJ: J Biol Chem 256:9605, 1981.PubMedGoogle Scholar
  63. 24.
    Weiss JB, Brown RA, Kumar S, Phillips P: Br J Cancer 40:498, 1979.Google Scholar
  64. 25.
    Gross JL, Moscatelli D, Jaffe EA, Rifkin DB: J Cell Biol 95:974–981, 1982.PubMedCrossRefGoogle Scholar
  65. 26.
    Knighton DR, Hunt TK, Thakral KK, Goodson WH III: Ann Surg 196:379–388, 1982.PubMedCrossRefGoogle Scholar
  66. 27.
    Wissler JH, Renner H: Immunobiol 14:438, 1982.Google Scholar
  67. 28.
    D’Amore PA, Glaser BM, Brunson SK, Fenselau AH: Proc Natl Acad Sci USA 78:3068–3072, 1981.PubMedCrossRefGoogle Scholar
  68. 29.
    Taylor S, Folkman J: Nature 297:307–312, 1982.PubMedCrossRefGoogle Scholar
  69. 30.
    Folkman J, Langer R, Linhardt RJ, Haudenschild C, Taylor S: Science 221:719–725, 1983.PubMedCrossRefGoogle Scholar

Copyright information

© Martinus Nijhoff Publishers, Boston 1984

Authors and Affiliations

  • Gerald W. Chodak
  • Judah Folkman

There are no affiliations available

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