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Inhibitors of Neovascularization: Critical Mediators in the Coordinate Regulation of Angiogenesis

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Angiogenesis

Part of the book series: NATO ASI Series ((NSSA,volume 263))

Abstract

The processes of tissue regeneration and repair, the cyclical proliferation of the nutrient-rich endometrial lining in preparation for implantation of the fertilized egg; and the complex developmental program that characterizes embryogenesis are biological processes that are strictly dependent on the rapid yet temporary ingrowth of new capillary blood vessels. In contrast, disorders such as neoplasia, proliferative vascular lesions, rheumatoid arthritis and psoriasis, and glaucoma are all characterized by disregulated angiogenesis. The mechanisms underling inappropriate neovascularization have been the subject of considerable investigation. Although there is ample evidence implicating the “overproduction” of normal and/or aberrant forms of angiogenic mediators in the pathogenesis of several well characterized disorders, only recently has attention been given to the role of naturally occurring inhibitors of angiogenesis and the consequences that result from a deficiency in the production of one or more of these “angiostatic” mediators (Moses and Langer, 1991a; Bouck, 1990 and 1993; DiPietro and Polverini, 1993, in press). This report will describe recent studies that support the assertion that angiogenesis is a process that is dependent upon the coordinate production of growth stimulatory and inhibitory molecules and that any disruption in this finely tuned regulatory circuit can result in the development of a number of diseases now classified as “angiogenesisdependent”.

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References

  • Bader, S.A., Fasching, C., Brodeur, G.M., and Stanbridge, E.J., Dissocoation of suppression of tumorigenicity and differentiation in vitro effected by transfer of a single human chromosome into neuroblastoma cells. Cell Growth Differ. 2: 245.

    Google Scholar 

  • Blood, C.H., and Zetter, B.R., 1990, Tumor interactions with the vasculature: Angiogenesis and tumor metastasis. Biochim. Biophys. Acta 1032: 89

    Google Scholar 

  • Bornstein, P., 1992, Thrombospondins: structure and regulation of expression. FASEB Jr. 6: 3290.

    CAS  Google Scholar 

  • Bouck, N., 1990, Tumor angiogenesis: the role of oncogenes and tumor suppressor genes. Cancer Cells 2, 179.

    PubMed  CAS  Google Scholar 

  • Bouck, N., Angiogenesis: a mechanism by which oncogenes and tumor suppressor genes regulate tumorigenesis, in “ Oncogenes and Tumor Suppressor Genes” C.C. Benz and E.T. Liu, eds, Kluwer Academic Publishers, Boston

    Google Scholar 

  • Bouck, N. P., Stoler, A. and Polverini, P. J., 1986, Coordinate control of anchorage independence, actin cytoskeleton and angiogenesis by human chromosome 1 in hamster-human hybrids. Cancer Res. 46: 5101.

    PubMed  CAS  Google Scholar 

  • Brem, H., and Folkman, J., 1975, Inhibition of tumor angiogenesis mediated by cartilage. J. Exp. Med. 141: 427.

    Article  PubMed  CAS  Google Scholar 

  • Brem, S., Preis, I., Langer, R., Folkman, J., and Patz, A., 1977, Inhibition of neovascularization by an extract derived from vitreous. Am. J. Ophthalmol. 84: 323.

    PubMed  Google Scholar 

  • Cozzolino, F., Torcia, M., Aldinucci, D., Ziche, M., Almerigogna, F., Bani, D., and Stern, D.M., 1990, Interleukin 1 is an autocrine regulator of human endothelial cell growth. Proc. Natl. Acad. Sci. USA., 87: 6487.

    Article  PubMed  CAS  Google Scholar 

  • Crum, R., Sazbo, S., and Folkman, J., 1985, A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment. Science 230: 1375.

    Article  PubMed  CAS  Google Scholar 

  • DiPietro, L. A., and Polverini, P.J., 1993, Role of the macrophage in the positive and negative regulation of wound neovascularization, Behring Inst. Mitt., (in press)

    Google Scholar 

  • DiPietro, L. A., Nebgen, D. R., and Polverini, P.J., [submitted for publication (a)]. Down-regulation of endothelial cell thrombospondin 1 enhances in vitro angiogenesis

    Google Scholar 

  • DiPietro, L. A., and Polverini, P. J., 1993, Angiogenic macrophages produce the angiogenic modulator thrombospondin 1. Am. J. Pathol. in press

    Google Scholar 

  • Eisenstein, R., Kuettner, K.E., Neopolitan, C., Sobel, L.W., and Sorgente, N., 1975, 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.

    PubMed  CAS  Google Scholar 

  • Engerman R.L., Pfaffenbach, D., and Davis, M.D., 1967, Cell turnover of capillaries. Lab. Invest. 17: 738.

    PubMed  CAS  Google Scholar 

  • Folkman, J., 1972, Angiogenesis in psoriasis: Therapeutic implications. J. Invest. Dermatol. 59: 40.

    Article  PubMed  CAS  Google Scholar 

  • Folkman, J., and Klagsbrun, M., 1987, Angiogenic factors. Science 235: 442.

    Article  PubMed  CAS  Google Scholar 

  • Folkman, J., Weisz, P. B., Joullie, M. M., Li, W. W., and Ewing, W. R., 1989, Control of angiogenesis wiyh systemic heparin substitutes. Scienec 243: 1490.

    Article  CAS  Google Scholar 

  • Frazier, W. A., 1987, Thrombospondin: a modular adhesive glycoprotein of platelets and nucleated cells. J. Cell Biol. 105: 625.

    Article  PubMed  CAS  Google Scholar 

  • Frazier, W. A., 1991, Thrombospondin. Curr. Opinions in Cell Biol. 3: 792.

    Google Scholar 

  • Goldfarb, M., 1990, The fibroblast growth factor family. Cell Growth Differ. 1: 439.

    PubMed  CAS  Google Scholar 

  • Good, D. J., Polverini, P. J., Rastinejad, F., Le Beau, M. M., Lemons, R. S., Frazier, W. A., and Bouck, N. P., 1990, A tumor suppressor-dependent inhibitor of angiogenesis is immunologically and functionally indistinguishable from a fragment of thrombospondin. Proc. Natl. Acad. Sci. USA 87: 6624.

    Google Scholar 

  • Grant, D. K., Tashiro, K-I., Segui-Real, B., Yamada, Y., Martin, G. R., and Kleinman, H. K., 1989, Two different laminin domains mediate the differentiation of human endothelial cells into capillary-like structures in vitro. Cell 58: 933.

    Article  PubMed  CAS  Google Scholar 

  • Haynes, W. L., Proia, A. D., and Klintworth, G. K., 1989, Effect of inhibitors of arachidonic acid metabolism on corneal neovascularization in the rat. Invest. Ophthalmol Visual Sci. 30: 1588.

    Google Scholar 

  • Hogg, P.J., Stenflo, J., and Mosher, D. F., 1992, Thrombospondin is a slow tight-binding inhibitor of plasmin. Biochemistry 31: 265.

    Article  PubMed  CAS  Google Scholar 

  • Huang, H-J.S., Yee, J-K., Shew, J-Y., Chen, P-L., Bookstein, R., Friedman, T., Lee, E.YH.P., and Lee, W-H., 1988, Suppression of the neoplastic phenotype by replacement of the RB gene in human cancer cells. Science 242: 1563.

    Article  PubMed  CAS  Google Scholar 

  • Ingber, D., and Folkman, J., 1988, Inhibition of angiogenesis through modulation of collagen metabolism. Lab. Invest. 59: 44.

    PubMed  CAS  Google Scholar 

  • Inoue, K., Korenaga, H., Tahnaka, N. G., Sakamoto, N., and Shizuo, K., 1988, The sulfated polysaccharide-peptidoglycan complex potently inhibits embryonic angiogenesis and tumor growth in the presence of cortisone acetate. Carbohydr. Res. 181: 135.

    Article  PubMed  CAS  Google Scholar 

  • Iruela-Arispe, M., Bornstein, P., and Sage, H., 1991, Thrombospondin exerts an antiangiogenic effect on cord formation by endothelial cells in vitro. Proc. Natl. Acad. Sci. USA 88: 5026.

    Article  PubMed  CAS  Google Scholar 

  • Jaffe, E. A., Ruggiero, J. T., and Falcone D. J., 1985, Monocytes and macrophages synthesize and secrete thrombospondin. Blood 65: 79.

    PubMed  CAS  Google Scholar 

  • Klagsbrun, M., and D’Amore P.A., 1991, Regulators of angiogenesis. Annu. Rev. Physiol. 53: 217.

    Article  PubMed  CAS  Google Scholar 

  • Klagsbrun, M., and Folkman, J., 1990, Peptide Growth Factors and Their Receptors II, in: “Angiogenesis. Handbook of Experimental Pharmacology, Vol., 95/II”, p. 549–586. M.B. Sporn and A.B. Roberts, (Eds.) Springer-Verlag, Berlin, Heildelberg, Germany.

    Google Scholar 

  • Koch, A. E., Polverini, P. J., and Leibovich, S. J., 1986, Stimulation of neovascularization by human rheumatoid synovial tissue macrophages. Arth. Rheum. 29: 471.

    Article  CAS  Google Scholar 

  • Koch, A. E.,Polverini, P.J., Kunkel, S. L., Harlow, L. A., DiPietro, L. A., Elner, V.M., Elner, S.G., and Strieter, R.M., 1992, Interleukin-8 (IL-8) as a macrophage-derived mediator of angiogenesis. Science 258: 1798.

    Article  PubMed  CAS  Google Scholar 

  • Langer, R., Brem, H., Falterman, K., Klein, M., and Folkman, J., 1976, Isolation of a cartilage factor that inhibits tumor neovascularization Science 193: 70.

    CAS  Google Scholar 

  • Lawler, J., 1986, The structural and functional properties of thrombospondin. Blood 67: 1197.

    PubMed  CAS  Google Scholar 

  • Lee, A., and Langer, R., 1983, Shark cartilage contains inhibitors of tumor angiogenesis. Science 221: 1185.

    Article  PubMed  CAS  Google Scholar 

  • Lutty, G. A., Thompson, D. C., Gallup, J. Y., Mello, R. J., Patz, A., and Fenselau, A., 1983, Vitreous: an inhibitor of retinal extract-induced neovascularization. Invest. Ophthalmol. Vis. Sci. 24: 52.

    PubMed  CAS  Google Scholar 

  • Lynch, N. R., Castes, M., Astoin, M., and Salomon, J. C., 1978, Mechanisms of inhibition of tumor growth by asprin and indomethacin. Br. J. Cancer 38: 503.

    Article  PubMed  CAS  Google Scholar 

  • Maione, T. E., Gray, G. S., Petro, J., Hunt, A. J., Donner, A. L., Bauer, S. I., Carson, H. F., and Sharpe, R. J., 1990, Inhibition of angiogenesis by recombinant human platelt factor-4 and related peptides. Science 247: 77.

    Article  PubMed  CAS  Google Scholar 

  • Mansfield, P. J., Boxer, L. A., and Suchard, S. J., 1990, Thrombospondin stimulates motility of human neutrophils. J. Cell Biol. 111: 3077.

    Article  PubMed  CAS  Google Scholar 

  • Moroco, J.R., Solt, D.B., and Polverini, P.J., 1990, Sequential loss of suppressor genes for three specific functions during in vivo carcinogenesis. Lab. Invest. 63: 298.

    PubMed  CAS  Google Scholar 

  • Moses, M.A., and Langer, R., 1991a, Inhibitors of angiogenesis. Biotechnology 9: 630.

    Article  PubMed  CAS  Google Scholar 

  • Moses, M. A., and Langer, R., 1991b, A metalloproteinase inhibitor as an inhibitor of neovascularization. J. Cell. Biochem. 47: 230.

    Article  PubMed  CAS  Google Scholar 

  • Nathan, C. F. (1987) Secreted products of macrophages. J. Clin. Invest. 79, 319–26.

    Article  PubMed  CAS  Google Scholar 

  • Nickoloff, B. J., Mitra, R. S., Varani, J., Dixit, V. M., and Polverini, P. J. (submitted for publication) Psoriatic keratinocyte induced angiogenesis is inhibited by hrombospondin.

    Google Scholar 

  • O’Shea, K. S., and Dixit, V. M., 1988, Unique distribution of the extracellular matrix component thrombospondin in the developing mouse embryo. J. Cell Biol. 107: 27–37.

    Google Scholar 

  • Oikawa, T., Hirotani, K., Nakamura, O., Shudo, K., Hiragun, A., and Iwaguchi, T., 1989, A highly potent antiangiogenic activity of retinoids. Cancer Lett. 48: 157

    Article  PubMed  CAS  Google Scholar 

  • Orchard, P. J., Smith, C. M. II, Woods, W. G., Day, D. L., and Dehner, L. P., 1989, Treatment of hemangioendotheliomas with alpha interferon. The Lancet 2: 565.

    Article  CAS  Google Scholar 

  • Pauli, B., Memoli, V., and Kuttner, K., 1981, Regulation of tumor invasion by cartilage-derived anti-invasive factor in vitro. J. Natl. Cancer Inst. 67: 65.

    PubMed  CAS  Google Scholar 

  • Peterson, H-I., 1986, Tumor angiogenesis inhibition by prostaglandin synthetase inhibitors. Anticancer Res. 6: 251.

    PubMed  CAS  Google Scholar 

  • Polverini, P. J., 1989, Macrophage-induced Angiogenesis: A review; in, “Macrophage- Derived Cell Regulatory Factors”, C. Sorg, ed., S. Karger, Basel, pp. 54

    Google Scholar 

  • Rastinejad, F., Polverini, P. J. and Bouck N. P., 1989, Regulation of the activity of a new inhibitor of angiogenesis by a cancer suppressor gene. Cell 56: 345.

    Article  PubMed  CAS  Google Scholar 

  • Robin, J. B., Regis-Pacheco, L. F., Kash, R. L., and Schanzlin, D. J., 1985, The histopathology of of corneal neovascularization, inhibitor effects. Arch Ophthalmol. 103: 284.

    Article  PubMed  CAS  Google Scholar 

  • Sage, H., and Bornstein, P., 1982, Endothelial cells from umbilical vein and a hemangioendothelioma secrete basement membrane largely to the exclusion of interstitial procollagens. Arteriosclerosis 2: 27.

    Article  PubMed  CAS  Google Scholar 

  • Sage, H., and Bornstein, P., 1991, Extracellular proteins that modulate cell-matrix interactions. J Biol. Chem. 266: 14831.

    PubMed  CAS  Google Scholar 

  • Savill, J., Hogg, N., and Haslett, C., 1991, Macrophage vitronectin receptor, CD36, and thrombospondin cooperate in recognition of neutrophils undergoing programmed cell death. Chest 99: 65.

    Article  Google Scholar 

  • Shapiro, R., and Valee, B. L., 1987, Human placental ribonuclease inhibitor abolishes both angiogenic and ribonucleolytic activities of angiogenin. Proc. Natl. Acad. Sci. 84: 22–38.

    Google Scholar 

  • Sidky, Y. A., and Borden, E. C., 1987, Inhibition of angiogenesis by interferons: effects on tumor-and lymphocyte-induced vascular responses. Cancer Res. 47: 51–55.

    Google Scholar 

  • Silverstein, R. L., and Nachman, R. L., 1987, Thrombospondin binds to monocytes and macrophages and mediates platelet-monocyte adhesion. J. Clin. Invest. 79: 867.

    Article  PubMed  CAS  Google Scholar 

  • Strieter, R. M., Kunkel, S. L., Elner, V. M., Martonyi, C. L., Koch, A. E., Polverini, P. J., and Elner, S. G., 1992, Interleukin-8 a corneal factor that induces neovascularization. Am. J. Pathol. 141: 1279.

    PubMed  CAS  Google Scholar 

  • Tannock, I. F., and Hayashi, S., 1972, The proliferation of capillary endothelial cells. Cancer Res. 32: 77.

    PubMed  CAS  Google Scholar 

  • Taylor, C. W., and Weiss, J. B., 1985, Partial purification of a 5.7k glycoprotein from bovine vitreous which inhibits both angiogenesis and collagenase activity. Biochem and Biophys. Res. Commun. 133: 911.

    Article  CAS  Google Scholar 

  • Taylor, S., and Folkman, J., 1982, Protamine is an inhibitor of angiogenesis. Nature 297: 307.

    Article  PubMed  CAS  Google Scholar 

  • Thomas, K.A., 1988, Transforming potential of fibroblast growth factor genes. Trends in Biochem. Sci. 13: 327.

    Article  Google Scholar 

  • Tolsma, S.S., Volpert, O.V., Good, D.J., Frazier, W.A., Polverini, P.J., and Bouck, N., 1993, Peptides derived from two separate domains of the matrix protein thrombospondin-1 have anti-angiogenic activity, J. Cell Biol. in press.

    Google Scholar 

  • West, D. C., and Kumar, S., 1989, Hyaluronan and Angiogenesis, in, The Biology of Hyaluronan ( Ciba Foundation Symp.) Wiley, Chichester, pp 143.

    Google Scholar 

  • White, C. W., Wolf, S. J., Korones, D. N., Sondheimer, H. M., Tosi, M. F., and Yu, A., 1991, Treatment of childhood angiomatous diseases with recombinant interferon alpha. J. Pediatr. 118: 59.

    Article  PubMed  CAS  Google Scholar 

  • Woltering, E. A., Barrie, R., O’Dorisio, T. M., Arce, D., Ure, T., Cramer, A., Holmes, D., Robertson, J., and Fassler, J., 1991, Somatostatin analogues inhibit angiogenesis in the chick chorioallantoic membrane. J. Surg. Res. 50: 245.

    Article  PubMed  CAS  Google Scholar 

  • Ziche, M., Jones, J., and Gullino, P. M., 1982, Role of prostaglandin El and copper in angiogenesis. J. Natl. Cancer Inst. 69: 475.

    PubMed  CAS  Google Scholar 

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Polverini, P.J. (1994). Inhibitors of Neovascularization: Critical Mediators in the Coordinate Regulation of Angiogenesis. In: Maragoudakis, M.E., Gullino, P.M., Lelkes, P.I. (eds) Angiogenesis. NATO ASI Series, vol 263. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9188-4_4

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  • DOI: https://doi.org/10.1007/978-1-4757-9188-4_4

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