Angiogenesis and Angiogenic Factors of Gastric Cancer

  • Yutaka Takahashi
  • Masayoshi Mai


Gastric cancer prognosis depends on the pathologic tumor type and the stage of disease [1,2]. Intestinal-type gastric cancer tends to be exophytic, metastasizing to the liver by hematogenous dissemination. In contrast, diffuse-type gastric cancer is more invasive, with predominantly peritoneal dissemination. The factors responsible for liver metastasis and peritoneal dissemination have not yet been identified.


Gastric Cancer Vascular Endothelial Growth Factor Vascular Endothelial Growth Factor Expression Vascular Endothelial Growth Factor Gene Survival Gain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Nishi M, Tamura T (1962) Clinical study of stomach cancer with hepatic metastasis. Jpn J Cancer Clin 8:422–433 (in Japanese)Google Scholar
  2. 2.
    Duarte I, Llanos O (1981) Patterns of metastases in intestinal and diffuse types of carcinoma of the stomach. Hum Pathol 12:237–242PubMedCrossRefGoogle Scholar
  3. 3.
    Folkman J (1986) How is blood vessel growth regulated in normal and neoplastic tissue? G. H. A. Clowes memorial award lecture. Cancer Res 46:467–473PubMedGoogle Scholar
  4. 4.
    Liotta L, Kleinerman J, Saldel G (1974) Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation. Cancer Res 34:997–1004PubMedGoogle Scholar
  5. 5.
    Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis: correlation in invasive breast carcinoma. N Engl J Med 324:1–8PubMedCrossRefGoogle Scholar
  6. 6.
    Macchiarini P, Fontanini G, Hardin MJ, Squartini F, Angeletti CA (1992) Relation of neovascularization to metastasis of non-small-cell lung cancer. Lancet 340:145–146PubMedCrossRefGoogle Scholar
  7. 7.
    Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J (1993) Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol 143:401–409PubMedGoogle Scholar
  8. 8.
    Graham CH, Rivers J, Kerbel RS, Stankiewicz KS, White WL (1994) Extent of vascularization as a prognostic indicator in thin (<0.76mm) malignant melanomas. Am J Pathol 145:510–514PubMedGoogle Scholar
  9. 9.
    Smith-McCune KK, Weidner N (1994) Demonstration and characterization of the angiogenic properties of cervical dysplasia. Cancer Res 54:800–804PubMedGoogle Scholar
  10. 10.
    Takahashi Y, Kitadai Y, Bucana CD, Cleary KR, Ellis LM (1995) Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res 55:3964–3968PubMedGoogle Scholar
  11. 11.
    Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306PubMedCrossRefGoogle Scholar
  12. 12.
    Ferrara N, Houck K, Jakeman L, Leung DW (1992) Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev 13:18–32PubMedGoogle Scholar
  13. 13.
    Folkman J, Klagsbrun M (1987) Angiogenic factors. Science 235:442–447PubMedCrossRefGoogle Scholar
  14. 14.
    New B, Yeoman L (1992) Identification of basic fibroblast growth factor sensitivity and receptor and ligand expression in human colon tumor cell lines. Cell Physiol 150:320–326CrossRefGoogle Scholar
  15. 15.
    Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Senger DR, Dvorak HF (1993) Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res 53:4727–4735PubMedGoogle Scholar
  16. 16.
    Millauer B, Wizigmann-Voos S, Achnurch H, Martinez R, Moller NPH, Risau W, Ullrich A (1993) High affinity VEGF binding and developmental expression suggest KDR as a major regulator of vasculogenesis and angiogenesis. Cell 72:835–846PubMedCrossRefGoogle Scholar
  17. 17.
    Brown LF, Berse B, Jackman RW, Tognazzi K, Guidi AJ, Dvorak HF, Senger DR, Connolly JL, Schnitt SJ (1995) Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer. Hum Pathol 26:86–91PubMedCrossRefGoogle Scholar
  18. 18.
    Samoto K, Ikezaki K, Ono M, Shono T, Kohno K, Kuwano M, Fukui M (1995) Expression of vascular endothelial growth factor and its possible relation with neovascularization in human brain tumors. Cancer Res 55:1189–1193PubMedGoogle Scholar
  19. 19.
    Takahashi Y, Kitadai Y, Bucana CD, Cleary KR, Ellis LM (1995) Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res 55:3964–3968PubMedGoogle Scholar
  20. 20.
    Kitadai Y, Ellis LM, Takahashi Y, Bucana CD, Anzai H, Tahara E, Fidler IJ (1995) Mutiparametric in situ messenger RNA hybridization analysis to detect metastasis-related genes in surgical specimens of human colon carcinomas. Clin Cancer Res 1:1095–1102PubMedGoogle Scholar
  21. 21.
    Takahashi Y, Tucker SL, Kitadai Y, Koura AN, Bucana CD, Cleary KR, Ellis LM (1997) Vessel counts and VEGF expression as prognostic factors in node-negative colon cancer. Arch Surg 132:541–546PubMedCrossRefGoogle Scholar
  22. 22.
    Takahashi Y, Cleary KR, Mai M, Kitadai Y, Bucana CD, Ellis LM (1996) Significance of vessel count and vascular endothelial growth factor and its receptor (KDR) in intestinal-type gastric cancer. Clin Cancer Res 2:1679–1684PubMedGoogle Scholar
  23. 23.
    Miyazono K, Okabe T, Urabe A, Takaku F, Heldin C-H (1987) Purification and properties of an endothelial cell growth factor from human platelets. J Biol Chem 262:4008–4103Google Scholar
  24. 24.
    Ishikawa F, Miyazono K, Hellman U, Drexler H, Wemstedt C, Hagiwara I, Usuki K, Takaku F, Risau W, Heldin CH (1989) Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature 338:557–562PubMedCrossRefGoogle Scholar
  25. 25.
    Moghaddam A, Bicknell R (1992) Expression of platelet-derived endothelial cell growth factor in Escherichia coli and confirmation of its thymidine Phosphorylase activity. Biochemistry 31:12141–12146PubMedCrossRefGoogle Scholar
  26. 26.
    Zimmerman M, Seidenberg J (1964) Deoxyribosyl transfer. 1. Thymidine Phosphorylase and nucleoside deoxyribosyltransferase in normal and malignant tissues. J Biol Chem 239:2618–2621PubMedGoogle Scholar
  27. 27.
    Pauly JL, Schuller MG, Zelcer AA, Kirss TA, Gore SS, Germain MJ (1977) Identification and comparative analysis of thymidine Phosphorylase in the plasma of healthy subjects and cancer patients. J Natl Cancer Inst 58:1587–1590PubMedGoogle Scholar
  28. 28.
    Yoshimura T, Matsushima K, Tanaka S, Robinson EA, Appella E, Oppenheim JJ, Leonard EJ (1987) Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci USA 84:9233–9237PubMedCrossRefGoogle Scholar
  29. 29.
    Reynolds K, Frazaneh F, Collins WP, Campbell S, Bourne TH, Lawton F, Moghaddam A, Harris AL, Bicknell R (1994) Correlation of ovarian malignancy with expression of platelet-derived endothelial cell growth factor. J Natl Cancer Inst 86:1234–1238PubMedCrossRefGoogle Scholar
  30. 30.
    O’Brien T, Cranston D, Fuggle S, Bicknell R, Harris AL (1995) Different angiogenic pathways characterize superficial and invasive bladder cancer. Cancer Res 55:510–513Google Scholar
  31. 31.
    Baird A, Momede P, Bohlen P (1985) Immunoreactive fibroblast growth factor in cells of peritoneal exudate suggests its identity with macrophage-derived growth factor. Biochem Biophys Res Commun 126:358–364PubMedCrossRefGoogle Scholar
  32. 32.
    Madtes DK, Raines EW, Sakariassen KS, Assoian RK, Sporn MB, Bell GI (1988) Imduction of transforming growth factor-α in activated human alveolar macrophages. Cell 53:285–293PubMedCrossRefGoogle Scholar
  33. 33.
    Martinet Y, Bitterman PB, Mornex J-F, Grotendorst GR, Martin GR, Crystal RG (1986) Activated human monocytes express the c-sis proto-oncogene and release a mediator showing pdgf-like activity. Nature 319:158–160PubMedCrossRefGoogle Scholar
  34. 34.
    Berse B, Brown LF, van DeWater L, Dvorak HA, Senger DR (1992) Vascular permeability factor (vascular endothelial growth factor) is expressed differentially m normal tissues, macrophages, and tumors. Mol Biol Cell 3:211–220PubMedGoogle Scholar
  35. 35.
    Polverini PJ, Leibovich SJ (1984) Induction of neovascularization in vivo and endothelial proliferation in vitro by tumor-associated macrophages. Lab Invest 51:635–642PubMedGoogle Scholar
  36. 36.
    Leibovich S, Polverini P, Shepard H, Wiseman D, Shively V, Nuseir N (1987) Macrophage-induced angiogenesis is mediated b tumor necrosis factor-α. Nature 329:630–632PubMedCrossRefGoogle Scholar
  37. 37.
    Griffiths L, Dachs GU, Bicknell R, Harris AL, Stratford IJ (1997) The influence of oxygen tension and pH on the expression of platelet-derived endothelial cell growth factor/thymidine phosphoryl in human breast tumor cells grown in vitro and in vivo. Cancer Res 57:570–572PubMedGoogle Scholar
  38. 38.
    Levy AP, Levy NS, Wegner S, Goldberg MA (1995) Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J Biol Chem 270:13333–13340PubMedCrossRefGoogle Scholar
  39. 39.
    Liu Y, Cox SR, Morita T, Kourembanas S (1995) Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells: idenification of a 5′ enhancer. Circ Res 77:638–643PubMedCrossRefGoogle Scholar
  40. 40.
    Eda H, Fujimoto K, Watanabe S, Ufa M, Hino A, Tanaka Y, Wada K, Ishitsuka H (1993) Cytokines induce thymidine Phosphorylase expression in tumor cells and make them more susceptible to 5′-deoxy-5-fluoridine. Cancer Chemother Pharmacol 32:333–338PubMedCrossRefGoogle Scholar
  41. 41.
    Li J, Perrell MA, Tsai JC, Yet SF, Hsieh CM, Yoshizumi M, Patterson C, Endege WO, Zhou F, Lee M-E (1995) Induction of vascular endothelial growth factor gene expression by interleukin-1β in rat aortic smooth muscle cells. J Biol Chem 270:308–312PubMedCrossRefGoogle Scholar
  42. 42.
    Kim KJ, Li B, Winer J, et al (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis supresses tumor growth in vivo. Nature 362:841PubMedCrossRefGoogle Scholar
  43. 43.
    Asano M, Yukita A, Matsumoto T, et al (1995) Inhibition of tumor growth and metastasis by an immunoneutralizing monoclonal antibody to human vascular endothelial growth factor/vascular permeability factor 121. Cancer Res 55:5296PubMedGoogle Scholar
  44. 44.
    Takahashi Y, Nishioka K (1995) Survival without tumor shrinkage: reevaluation of survival gain by cytostatic effect of chemotherapy. J Natl Cancer Inst 87:1262–1263PubMedGoogle Scholar
  45. 45.
    Nemunaitis J, Poole C, Primrose J, Rosemurgy A, Malfetano J, Brown P, Berrington A, Cornish A, Lynch K, Rasmussen H, Kerr D, Cox D, Millar A (1998) Combined analysis of studies of the effects of the matrix metalloproteinase inhibitor marimastat on serum tumor markers in advanced cancer: selection of a biological active and tolerable dose for longer-term studies. Clin Cancer Res 4:1101–1109PubMedGoogle Scholar

Copyright information

© Springer Japan 1999

Authors and Affiliations

  • Yutaka Takahashi
    • 1
  • Masayoshi Mai
    • 1
  1. 1.Surgical Oncology, Cancer Research InstituteKanazawa UniversityKanazawaJapan

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