Angiogenesis pp 99-112 | Cite as

Autocrine Role of Basic Fibroblast Growth Factor (bFGF) in Angiogenesis and Angioproliferative Diseases

  • Anna Gualandris
  • Patrizia Dell’Era
  • Marco Rusnati
  • Roberta Giuliani
  • Elena Tanghetti
  • Maria Pia Molinari-Tosatti
  • Marina Ziche
  • Domenico Ribatti
  • Marco Presta
Chapter
Part of the NATO ASI Series book series (NSSA, volume 298)

Abstract

bFGF belongs to the family of the heparin-binding growth factors (Basilico and Moscatelli, 1992). The single copy human bFGF gene encodes multiple bFGF isoforms with molecular weights ranging from 24 kD to 18 kD. High molecular weight isoforms (HMW-bFGFs) are colinear NH2-terminal extensions of the better characterized 18 kD protein (Florkiewicz and Sommer, 1989). Both low and high molecular weight bFGFs exert angiogenic activity in vivo and induce cell proliferation, protease production, and Chemotaxis in endothelial cells in vitro (Gualandris, Urbinati, Rusnati, Ziche, and Presta, 1994). Also, bFGF has been shown to stimulate endothelial cells to form capillary-like structures in collagen gels (Montesano, Vassalli, Baird, Guillemin, and Orci, 1989) and to invade the amniotic membrane in vitro (Mignatti, Tauboi, Robbins, and Rifkin, 1989). Moreover, the phenotype induced in vitro by bFGF in endothelial cells includes modulation of integrin expression (Klein, Giancotti, Presta, Albelda, Buck, and Rifkin, 1993), gap-junctional intercellular communication (Pepper and Meda, 1992) and urokinase receptor upregulation (Mignatti, Mazzieri, and Rifkin, 1991a). Studies with neutralizing anti-bFGF antibodies have implicated endogenous bFGF in wound repair (Broadly, Aquino, Woodward, Bickley-Sturrock, Sat, Rifkin, and Davidson, 1989), vascularization of the chorioallantoic membrane during chick embryo development (Ribatti, Urbinati, Nico, Rusnati, Roncali, and Presta, 1995), and tumor growth under defined experimental conditions (Baird, Mormède, and Bohlen, 1986; Gross, Herblin, Dusak, Czerniak, Diamond, Sun, Eidsvoog, Dexter, and Yoayon, 1993).

Keywords

Basic Fibroblast Growth Factor Acquire Immune Deficiency Syndrome Amniotic Membrane Normal Endothelial Cell bFGF mRNA 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abraham, J.A., Mergia, A., Whang, J.L., Turnolo, A., Friedman, J., Hjerrild, J., Gospodarowicz, D., and Fiddes, J., 1986, Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor, Science 233:545–548.CrossRefPubMedGoogle Scholar
  2. Albini, A., Fontanini, G., Masiello, L., Tacchetti, C., Bigini, D., Luzzi, P., Noonan, D.M., and Stetler-Stevenson, W.G., 1994, Angiogenic potential in vivo by Kaposi sarcoma cell-free supernatants and HIVl-tat product: inhibition of KS-like lesions by TIMP-2. AIDS 8:1237–1244.CrossRefPubMedGoogle Scholar
  3. Baird, A., Mormède, P., and Bohlen, P., 1985, Immunoreactive fibroblast growth factor in cells of peritoneal exudate suggests its identity with macrophage-derived growth factor, Biochem. Biophys. Res. Commun. 126:358–364.CrossRefPubMedGoogle Scholar
  4. Baird, A., Mormède, P., and Bohlen, P., 1986, Immunoreactive fibroblast growth factor (FGF) in a transplantable chondrosarcoma: inhibition of tumor growth by antibodies to FGF, J. Cell. Biochem. 30:79–85.CrossRefPubMedGoogle Scholar
  5. Barillari, G., Buonaguro, L., Fiorelli, V., Hoffman, J., Michaels, F., Gallo, R.C., and Ensoli, B., 1992, Effects of cytokines from activated immune cells on vascular cell growth and HIV-1 gene expression, J. Immunol. 149:3727–3734.PubMedGoogle Scholar
  6. Basilico, C., and Moscatelli, D., 1992, The FGF family of growth factors and oncogenes, Adv. Cancer Res. 59:115–165.CrossRefPubMedGoogle Scholar
  7. Bastaki, M., Nelli, E.E., Dell’Era, P., Rusnati, M., Molinari Tosatti, M.P., Parolini, S., Aurbach, R., Ruco, L.P., Possati, L., and Presta, M., 1997, Basic firboblast growth factor-induced angiogenic phenotype in mouse endothelium. A study of aortic and microvascular endothelial cell lines, Arterioscler. Thromb. Vasc. Biol. 17:454–464.CrossRefPubMedGoogle Scholar
  8. Blotnick, S., Peoples, G.E., Freeman, Ml, Eberlein, T.J., and Klagsbrun, M., 1994, T lymphocytes synthesize and export heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor, mitogens for vascular cells and fibroblasts: differential production and release by CD4+ and CD8+ T cells, Proc. Natl. Acad. Sci. U.S.A. 91:2890–2894.CrossRefPubMedGoogle Scholar
  9. Broadly, K.N., Aquino, A.M., Woodward, S.C., Buckley-Sturrock, A., Sato, Y., Rifkin, D.B., and Davidson, J.M., 1989, Monospecific antibodies implicate basic fibroblast growth factor in normal wound repair, Lab. Invest. 61:571–575.Google Scholar
  10. Bussolino, F., De Rossi, M., Sica, A., Colotta, F., Wang, J.M., Bocchietto, E., Martin-Padura, I., Bosia, A., Dejana, E., and Mantovani, A., 1991, Murine endothelioma cell lines transformed by polyoma middle T oncogene as target for and producers of cytokines, J. Immunol. 147:2122–2129.PubMedGoogle Scholar
  11. Cozzolino, F., Torcia, M., Lucibello, M., Morbidelli, L., Ziehe, M., Platt, J., Fabiani, S., Brett, J., and Stern, D., 1993, Cytokine-mediated control of endothelial cell growth: interferon-α and interleukin-2 synergistically enhance basic fibroblast growth factor synthesis and induce release promoting cell growth in vitro and in vivo, J. Clin. Invest. 91:2504–2512.CrossRefPubMedGoogle Scholar
  12. DiMario, J., Buffinger, N., Yamada, S., and Strohman, R.C., 1989, Fibroblast growth factor in the extracellular matrix of dystrophic (mdx) mouse muscle, Science 244:688–690.CrossRefPubMedGoogle Scholar
  13. Ensoli, B., Gendelman, R., Markham, P., Fiorelli, V., Colombini, S., Raffeld, M., Cafaro, A., Chang, H.K., Brady, J.N., and Gallo, R.C., 1994a, Synergy between basic fibroblast growth factor and HIV-1 Tat protein in induction of Kaposi’s sarcoma, Nature 371:674–680.CrossRefPubMedGoogle Scholar
  14. Ensoli, B., Markham, P., Kao, V., Barillari, G., Fiorelli, V., Gendelman, R., Raffeld, M., Zon, G., and Gallo, R.C., 1994b, Block of AIDS-Kaposi’s sarcoma (KS) cell growth, angiogenesis, and lesion formation in nude mice by antisense oligonucleotide targeting basic fibroblast growth factor. A novel strategy for the therapy of KS, J. Clin. Invest. 94:1736–1746.CrossRefPubMedGoogle Scholar
  15. Enzinger, F.M., and Weiss S.W., 1995, Soft tissue tumors, pp. 579–677, Mosby-Year Book Inc., St. Louis.Google Scholar
  16. Fiorelli, V., Gendelman, R., Samaniego, F., Markham, P.D., and Ensoli, B., 1995, Cytokines from activated T cells induce normal endothelial cells to acquire the phenotypic and functional features of AIDS-Kaposi’s sarcoma spindle cells, J. Clin. Invest. 95:1723–1734.CrossRefPubMedGoogle Scholar
  17. Florkiewicz, R.Z., and Sommer, A., 1989, Human basic fibroblast growth factor gene encodes four polypeptides: three initiate translation from non-AUG codons, Proc. Natl. Acad. Sci. U.S.A. 86:3978–3981.CrossRefPubMedGoogle Scholar
  18. Folkman, J., Klagsbrun, M., Sasse, J., Wadzinski, M., Ingber, D., and Vlodavski, I., 1988. A heparin-binding angiogenic protein -basic fibroblast growth factor- is stored within basement membran, Am. J. Pathol 130:393–400.PubMedGoogle Scholar
  19. Gajdusek, C.M., and Carbon, S., 1989, Injury-induced release of basic fibroblast growth factor from bovine aortic endothelium, J. Cell. Physiol. 139:570–579.CrossRefPubMedGoogle Scholar
  20. Garlanda, C., Parravicini, C., Sironi, M., De Rossi, M., Wainstock de Calmanovici, R., Carozzi, F., Bussolino, F., Colotta, F., Mantovani A., and Vecchi, A., 1994, Progressive growth in immunodeficient mice and host cell recruitment by mouse endothelial cells transformed by polyoma middle-sized T antigen: implications for the pathogenesis of opportunistic vascular tumors, Proc. Natl. Acad. Sci. U.S.A. 91:7291–7295.CrossRefPubMedGoogle Scholar
  21. Gross, J.L., Herblin, W.F., Dusak, B.A., Czerniak, P., Diamond, M.D., Sun, T., Eidsvoog, K., Dexter, D.L., and Yayon, A., 1993, Effects of modulation of basic fibroblast growth factor on tumor growth in vivo, J. Natl. Cancer Inst. 85:121–131.CrossRefPubMedGoogle Scholar
  22. Gualandris, A., Urbinati, C., Rusnati, M., Ziehe, M., and Presta, M., 1994, Interaction of high molecular weight basic fibroblast growth factor (bFGF) with endothelium: biological activity and intracellular fate of human recombinant Mr 24,000 bFGF, J. Cell. Physiol. 161:149–159.CrossRefPubMedGoogle Scholar
  23. Gualandris, A., Rusnati, M., Belleri, M., Nelli, E.E., Bastaki, M., Molinari-Tosatti, MP., Bonardi, F., Parolini, S., Albini, A., Morbidelli, L., Ziche, M., Corallini, A., Possati, L., Vacca, A., Ribatti, D., and Presta, M., 1996a, Basic fibroblast growth factor overexpression in endothelial cells: an autocrine mechanism for angiogenesis and angioproliferative diseases, Cell Growth & Differ. 7:147–160.Google Scholar
  24. Gualandris, A., Rusnati, M., Belleri, M., Molinari-Tosatti, M.P., Bonardi, F., Parolini, S., Albini, A., Ziche, M., and Presta, M., 1966b, Angiogenic phenotype induced by basic fibroblast growth factor transfection in brain microvascular endothelial cells: an in vitro autocrine model of angiogenesis in brain tumors, Int. J. Oncol. 8:567–573.Google Scholar
  25. Hawker, J.R.H., and Granger, J., 1993, Tyrosine kinase inhibitors impair fibroblast growth factor signaling in coronary endothelial cells, Am J. Physiol. 266:H107–H120.Google Scholar
  26. Itoh, H., Mukoyama, M., Pratt, R.E., and Dzau, V.J., 1992, Specific blockade of basic fibroblast growth factor gene expression in endothelial cells by antisense oligonucleotide, Biochem. Biophys. Res. Commun. 188:1205–1213.CrossRefPubMedGoogle Scholar
  27. Jouanneau, J., Moens, G., Bourgeois, Y., Poupon, M.F., and Thiery, J.P., 1994, A minority of carcinoma cells producing acidic fibroblast growth factor induces a community effect for tumor progression, Proc. Natl. Acad Sci. U.S.A. 91:286–290.CrossRefPubMedGoogle Scholar
  28. Klein, S., Giancotti, F.G., Presta, M., Albelda, S.M., Buck, C.A., and Rifkin, D.B., 1993, Basic fibroblast growth factor modulates integrin expression in microvascular endothelial cells, Mol. Biol. Cell. 4:973–982.PubMedGoogle Scholar
  29. Levine, A.M., 1993, AIDS-related malignancies: the emerging epidemic, J. Natl. Cancer Inst. 85:1382–1387.CrossRefPubMedGoogle Scholar
  30. Mantovani, A., Bussolino, F., and Dejana, E., 1992, Cytokine regulation of endothelial cell function, FASEB J. 6:2591–2599.PubMedGoogle Scholar
  31. McNeil, P.L., Muthukrishnan, L., Warder, E., and D’Amore, P., 1989, Growth factors are released by mechanically wounded endothelial cells, J. Cell Biol. 109:811–822.CrossRefPubMedGoogle Scholar
  32. Mignatti, P., Tauboi, R., Robbins, E., and Rifkin, D.B., 1989, In vitro angiogenesis on the human amniotic membrane, requirement for basic fibroblast growth factor, J. Cell Biol. 108:671–682.CrossRefPubMedGoogle Scholar
  33. Mignatti, P., Mazzieri, R., and Rifkin, D.B., 1991a, Expression of the urokinase receptor in vascular endothelial cells is stimulated by basic fibroblast growth factor, J. Cell Biol. 113:1193–1201.CrossRefPubMedGoogle Scholar
  34. Mignatti, P., Morimoto, T., and Rifkin, D.B., 1991b, Basic fibroblast growth factor released by single, isolated cells stimulates their migration in an autocrine manner, Proc. Natl. Acad. Sci. U.S.A. 88:11007–11011.CrossRefPubMedGoogle Scholar
  35. Montesano, R., Vassalli, J.D., Baird, A., Guillemin, R., and Orci, L., 1986, Basic fibroblast growth factor induces angiogenesis in vitro, Proc. Natl. Acad. Sci. U.S.A. 83:7297–7301.CrossRefPubMedGoogle Scholar
  36. Moscatelli, D., Presta, M., Joseph-Silverstein, J., and Rifkin, D.B., 1986, Both normal and tumor cells produce basic fibroblast growth factor, J. Cell Physiol. 129:273–276.CrossRefPubMedGoogle Scholar
  37. Ohtani, H., Nakamura, S., Watanabe, Y., Mizoi, T., Saku, T., and Nagura, H., 1993, Immunocytochemical localization of basic fibroblast growth factor in carcinomas and inflammatory lesions of the human digestive tract, Lab. Invest. 68:520–527.PubMedGoogle Scholar
  38. Pepper, M.S., and Meda, P., 1992, Basic fibroblast growth factor increases junctional communication and connexin 43 expression in microvascular endothelial cells, J. Cell. Physiol. 153:196–205.CrossRefPubMedGoogle Scholar
  39. Pepper, M.S., Sappino, A.P., Stocklin, R., Montesano, R., Orci, L., and Vassalli, J.D., 1993, Upregulation of urokinase receptor expression on migrating endothelial cells, J. Cell Biol. 122:673–684.CrossRefPubMedGoogle Scholar
  40. Peverali, F.A., Mandriota, S.J., Ciana, P., Marelli, R., Quax, P., Rifkin, D.B., Delia Valle, G., and Mignatti, P., 1994, Tumor cells secrete an angiogenic factor that stimulates basic fibroblast growth factor and urokinase expression in vascular endothelial cells, J. Cell. Physiol. 161:1–14.CrossRefPubMedGoogle Scholar
  41. Presta, M., Moscatelli, D., Joseph-Silverstein, J., and Rifkin, D.B., 1986, Purification from a human hepatoma cell line of a basic fibroblast growth factor-like molecule that stimulates capillary endothelial cell plasminogen activator production, DNA synthesis, and migration, Mol Cell. Biol. 6:4060–4066.PubMedGoogle Scholar
  42. Presta, M., Maier, J.A.M., Rusnati, M., and Ragnotti, G., 1989, Basic fibroblast growth factor: production, mitogenic response, and post-receptor signal transduction in cultured normal and transformed fetal bovine aortic endothelial cells, J. Cell. Physiol. 141:517–526.CrossRefPubMedGoogle Scholar
  43. Ribatti, D., Urbinati, C., Nico, B., Rusnati, M., Roncali, L., and Presta, M., 1995, Endogenous basic fibroblast growth factor in the vascularization of the chick embryo chorioallantoic membrane, Dev. Biol. 170:39–49.CrossRefPubMedGoogle Scholar
  44. Rogelj, S., Klagsbrun, M., Atzmon, R., Kurokawa, M., Haimovitz, A., Fuks, Z., and Vlodavski, I., 1989, Basic fibroblast growth factor is an extracellular matrix component required for supporting the proliferation of vascular endothelial cells and the differentiation of PC12 cells, J. Cell Biol. 109:823–831.CrossRefPubMedGoogle Scholar
  45. Sato, Y., and Rifkin, D.B., 1988, Autocrine activities of basic fibroblast growth factor: regulation of endothelial cell movement, plasminogen activator synthesis, and DNA synthesis, J. Cell Biol. 107:1199–1205.CrossRefPubMedGoogle Scholar
  46. Salahuddin, S.Z., Nakamura, S., Biberfeld, P., Kaplan, M.H., Markham, P.D., Larsson, L., and Gallo, R.C., 1988, Angiogenic properties of Kaposi’s sarcoma-derived cells after long-term culture in vitro, Science 242:430–433.CrossRefPubMedGoogle Scholar
  47. Schulze-Osthoff, K., Risau, W., Vollmer, E., and Sorg, C., 1990, In situ detection of basic fibroblast growth factor by highly specific antibodies, Am. J. Pathol. 137:85–92.PubMedGoogle Scholar
  48. Schweigerer, L., Neufeld, G., Friedman, J., Abraham, J.A., Fiddes, J.C., and Gospodarowicz, D., 1987, Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth, Nature 325:257–259.CrossRefPubMedGoogle Scholar
  49. Speir, E., Tanner, V., Gonzales, A.M., Farris, J., Baird, A., and Casscells, W., 1992, Acid and basic fibroblast growth factors in adult rat heart myocytes: localization, regulatio in culture, and effects on DNA synthesis, Circ. Res. 71:251–259.CrossRefPubMedGoogle Scholar
  50. Statuto, M., Ennas, M.G., Zamboni, G., Bonetti, F., Pea, M., Bernardello, F., Pozzi, A., Rusnati, M., Gualandris, A., and Presta, M., 1993, Basic fibroblast growth factor in human pheochromocytoma: a biochemical and immunohistochemical study, Int. J. Cancer. 53:5–10.CrossRefPubMedGoogle Scholar
  51. Sturzl, M., Brandstetter, H., and Roth, W.K., 1992, Kaposi’s sarcoma, a review of gene expression and ultrastructure of KS spindle cells in vivo, AIDS Res. Human Retrov. 8:1753–1763.CrossRefGoogle Scholar
  52. Taraboletti, G., Belotti, D., Dejana, E., Mantovani, A., and Giavazzi, F., 1993, Endothelial cell migration and invasiveness are induced by a soluble factor produced by murine endothelioma cells transformed by polyoma virus middle T oncogene, Cancer Res. 53:3812–3816.PubMedGoogle Scholar
  53. Takahashi, J.A., Mori, H., Fukumoto, M., Igarashi, K., Jaye, M., Oda, Y., Kikuchi, H., and Hatanaka, M., 1990, Gene expression of fibroblast growth factors in human gliomas and meningiomas: demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissues, Proc. Natl. Acad. Sci. U.S.A. 87:5710–5714.CrossRefPubMedGoogle Scholar
  54. Takahashi, K., Mulliken, J.B., Kozakewich, H.P.W., Rogers, R.A., Folkman, J., and Ezekowitz, R.A.B., 1994, Cellular markers that distinguish the phases of hemangioma during infancy and childhood, J. Clin. Invest. 93:2357–2364.CrossRefPubMedGoogle Scholar
  55. Vlodavski, I., Folkman, J., Sullivan, R., Friedman, R., Ishai-Michaell, R., Sasse, J., and Klagsbrun, M., 1987a, Endothelial cell-derived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix, Proc. Natl. Acad. Sci. U.S.A. 84:2292–2296.CrossRefGoogle Scholar
  56. Vlodavski, I., Friedman, R., Sullivan, R., Sasse, J., and Klagsbrun, M., 1987b, Aortic endothelial cells synthesize basic fibroblast growth factor which remains cell associated and platelet-derived growth factor-like protein which is secreted, J. Cell. Physiol. 131:402–408.CrossRefGoogle Scholar
  57. Weich, H., Iberg, N., Klagsbrun, M., and Folkman, J., 1991, Transcriptional regulation of basic fibroblast growth factor gene expression in capillary endothelial cells, J. Cell. Biochem. 47:158–194.CrossRefPubMedGoogle Scholar
  58. Witte, L., Fuka, Z., Haimovitz, F.A., Vlodavski, I., Goodman, D.S., and Eldor, A., 1989, Effects of irradiation on the release of growth factors from cultured bovine, porcine, and human endothelial cells, Cancer Res. 49:5066–5072.PubMedGoogle Scholar
  59. Yamanaka, Y., Friess, H., Buchler, M., Beger, H.G., Uchida, E., Onda, M., and Kobrin, M.S., 1993, Overexpression of acidic and basic fibroblast growth factors in human pancreatic cancer correlates with advanced tumor stage, Cancer Res. 53:5289–5296.PubMedGoogle Scholar
  60. Zagzag, D., Miller, D.C., Sato, Y., Rifkin, D.B., and Burstein, D.E., 1990, Immunohistochemical localization of basic fibroblast growth factor in astrocytomas, Cancer Res. 50:7393–7398.PubMedGoogle Scholar
  61. Ziche, M., Parenti, A., Ledda, F., Dell’Era, P., Granger, H.J., Maggi, C.A., and Presta, M., 1997, Nitric oxide promotes proliferation and plasminogen activator production by coronary venular endothelium through endogenous bFGF, Circ. Res. in press.Google Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Anna Gualandris
    • 1
  • Patrizia Dell’Era
    • 1
  • Marco Rusnati
    • 1
  • Roberta Giuliani
    • 1
  • Elena Tanghetti
    • 1
  • Maria Pia Molinari-Tosatti
    • 2
  • Marina Ziche
    • 3
  • Domenico Ribatti
    • 4
  • Marco Presta
    • 1
  1. 1.Unit of General Pathology and ImmunologyUniversity of BresciaBresciaItaly
  2. 2.Unit of Histology, Department of Biomedical Sciences and BiotechnologyUniversity of BresciaBresciaItaly
  3. 3.Department of PharmacologyUniversity of FlorenceFlorenceItaly
  4. 4.Institute of Anatomy, Histology and EmbryologyUniversity of BariBariItaly

Personalised recommendations