Monoclonal antibodies against heparin-binding growth factor II/basic fibroblast growth factor that block its biological activity: invalidity of the antibodies for tumor angiogenesis.
Journal: 1990/January - Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
PUBMED: 2481318
Abstract:
Two monoclonal antibodies (mAbs) against bovine heparin-binding growth factor II (HBGF-II)/basic fibroblast growth factor (bFGF) were obtained from mouse hybridoma cell lines. They were highly specific for bFGF from bovine, human, and mouse sources and did not cross-react with bovine heparin-binding growth factor I (HBGF-I)/acidic fibroblast growth factor (aFGF). The immunoglobulin class and subclass of these mAbs were IgG1, K. The apparent dissociation constant (Kd) for bFGF of these mAbs ranged from 10(-9) to 10(-10) M. One mAb (bFM-2) also cross-reacted with heat-inactivated bFGF, while the other mAb (bFM-1) did not, suggesting that bFM-1 recognized the conformation of the bFGF molecule necessary for its biological activity. These mAbs inhibited growth of cultured bovine capillary endothelial cells in both the presence and absence of exogenous bFGF, indicating the autocrine action of this growth factor in in vitro growth of these cells. On the other hand, injection of these hybridoma cell lines s.c. into the backs of athymic mice resulted in development of highly vascularized solid tumors and a sustained high level of anti-bFGF activity in the blood of the tumor-bearing mice. These findings suggest that bFGF is not essential as an autocrine or paracrine growth factor for angiogenesis in vivo. These mAbs should be useful in further studies on the physiological role and the conformation-function relationship of bFGF because they block its biological activity.
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Proc Natl Acad Sci U S A 86(24): 9911-9915

Monoclonal antibodies against heparin-binding growth factor II/basic fibroblast growth factor that block its biological activity: invalidity of the antibodies for tumor angiogenesis.

Abstract

Two monoclonal antibodies (mAbs) against bovine heparin-binding growth factor II (HBGF-II)/basic fibroblast growth factor (bFGF) were obtained from mouse hybridoma cell lines. They were highly specific for bFGF from bovine, human, and mouse sources and did not cross-react with bovine heparin-binding growth factor I (HBGF-I)/acidic fibroblast growth factor (aFGF). The immunoglobulin class and subclass of these mAbs were IgG1, K. The apparent dissociation constant (Kd) for bFGF of these mAbs ranged from 10(-9) to 10(-10) M. One mAb (bFM-2) also cross-reacted with heat-inactivated bFGF, while the other mAb (bFM-1) did not, suggesting that bFM-1 recognized the conformation of the bFGF molecule necessary for its biological activity. These mAbs inhibited growth of cultured bovine capillary endothelial cells in both the presence and absence of exogenous bFGF, indicating the autocrine action of this growth factor in in vitro growth of these cells. On the other hand, injection of these hybridoma cell lines s.c. into the backs of athymic mice resulted in development of highly vascularized solid tumors and a sustained high level of anti-bFGF activity in the blood of the tumor-bearing mice. These findings suggest that bFGF is not essential as an autocrine or paracrine growth factor for angiogenesis in vivo. These mAbs should be useful in further studies on the physiological role and the conformation-function relationship of bFGF because they block its biological activity.

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  • Gospodarowicz D, Neufeld G, Schweigerer L. Fibroblast growth factor: structural and biological properties. J Cell Physiol Suppl. 1987;Suppl 5:15–26. [PubMed] [Google Scholar]
  • Fett JW, Strydom DJ, Lobb RR, Alderman EM, Bethune JL, Riordan JF, Vallee BL. Isolation and characterization of angiogenin, an angiogenic protein from human carcinoma cells. Biochemistry. 1985 Sep 24;24(20):5480–5486. [PubMed] [Google Scholar]
  • Schreiber AB, Winkler ME, Derynck R. Transforming growth factor-alpha: a more potent angiogenic mediator than epidermal growth factor. Science. 1986 Jun 6;232(4755):1250–1253. [PubMed] [Google Scholar]
  • Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, et al. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167–4171.[PMC free article] [PubMed] [Google Scholar]
  • Leibovich SJ, Polverini PJ, Shepard HM, Wiseman DM, Shively V, Nuseir N. Macrophage-induced angiogenesis is mediated by tumour necrosis factor-alpha. Nature. 1987 Oct 15;329(6140):630–632. [PubMed] [Google Scholar]
  • Fràter-Schröder M, Risau W, Hallmann R, Gautschi P, Böhlen P. Tumor necrosis factor type alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5277–5281.[PMC free article] [PubMed] [Google Scholar]
  • Esch F, Baird A, Ling N, Ueno N, Hill F, Denoroy L, Klepper R, Gospodarowicz D, Böhlen P, Guillemin R. Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6507–6511.[PMC free article] [PubMed] [Google Scholar]
  • Gospodarowicz D, Baird A, Cheng J, Lui GM, Esch F, Bohlen P. Isolation of fibroblast growth factor from bovine adrenal gland: physicochemical and biological characterization. Endocrinology. 1986 Jan;118(1):82–90. [PubMed] [Google Scholar]
  • Ueno N, Baird A, Esch F, Ling N, Guillemin R. Isolation of an amino terminal extended form of basic fibroblast growth factor. Biochem Biophys Res Commun. 1986 Jul 31;138(2):580–588. [PubMed] [Google Scholar]
  • Sommer A, Brewer MT, Thompson RC, Moscatelli D, Presta M, Rifkin DB. A form of human basic fibroblast growth factor with an extended amino terminus. Biochem Biophys Res Commun. 1987 Apr 29;144(2):543–550. [PubMed] [Google Scholar]
  • Abraham JA, Mergia A, Whang JL, Tumolo A, Friedman J, Hjerrild KA, Gospodarowicz D, Fiddes JC. Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor. Science. 1986 Aug 1;233(4763):545–548. [PubMed] [Google Scholar]
  • Abraham JA, Whang JL, Tumolo A, Mergia A, Friedman J, Gospodarowicz D, Fiddes JC. Human basic fibroblast growth factor: nucleotide sequence and genomic organization. EMBO J. 1986 Oct;5(10):2523–2528.[PMC free article] [PubMed] [Google Scholar]
  • Kurokawa T, Sasada R, Iwane M, Igarashi K. Cloning and expression of cDNA encoding human basic fibroblast growth factor. FEBS Lett. 1987 Mar 9;213(1):189–194. [PubMed] [Google Scholar]
  • Simpson RJ, Moritz RL, Lloyd CJ, Fabri LJ, Nice EC, Rubira MR, Burgess AW. Primary structure of ovine pituitary basic fibroblast growth factor. FEBS Lett. 1987 Nov 16;224(1):128–132. [PubMed] [Google Scholar]
  • Shimasaki S, Emoto N, Koba A, Mercado M, Shibata F, Cooksey K, Baird A, Ling N. Complementary DNA cloning and sequencing of rat ovarian basic fibroblast growth factor and tissue distribution study of its mRNA. Biochem Biophys Res Commun. 1988 Nov 30;157(1):256–263. [PubMed] [Google Scholar]
  • Nishikawa K, Yoshitake Y, Ikuta S. Derivation of monoclonal antibody to human epidermal growth factor. Methods Enzymol. 1987;146:11–22. [PubMed] [Google Scholar]
  • Massoglia SL, Kenney JS, Gospodarowicz DJ. Characterization of murine monoclonal antibodies directed against basic fibroblast growth factor. J Cell Physiol. 1987 Sep;132(3):531–537. [PubMed] [Google Scholar]
  • Gospodarowicz D, Cheng J, Lui GM, Baird A, Böhlent P. Isolation of brain fibroblast growth factor by heparin-Sepharose affinity chromatography: identity with pituitary fibroblast growth factor. Proc Natl Acad Sci U S A. 1984 Nov;81(22):6963–6967.[PMC free article] [PubMed] [Google Scholar]
  • Matuo Y, Nishi N, Muguruma Y, Yoshitake Y, Masuda Y, Nishikawa K, Wada F. Stabilization of fibroblast growth factors by a non-cytotoxic zwitterionic detergent, 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS). In Vitro Cell Dev Biol. 1988 May;24(5):477–480. [PubMed] [Google Scholar]
  • Yoshitake Y, Nishikawa K. Production of monoclonal antibodies with specificity for different epitopes on the human epidermal growth factor molecule. Arch Biochem Biophys. 1988 Jun;263(2):437–446. [PubMed] [Google Scholar]
  • Goetz IE, Warren J, Estrada C, Roberts E, Krause DN. Long-term serial cultivation of arterial and capillary endothelium from adult bovine brain. In Vitro Cell Dev Biol. 1985 Mar;21(3 Pt 1):172–180. [PubMed] [Google Scholar]
  • Kan M, DiSorbo D, Hou JZ, Hoshi H, Mansson PE, McKeehan WL. High and low affinity binding of heparin-binding growth factor to a 130-kDa receptor correlates with stimulation and inhibition of growth of a differentiated human hepatoma cell. J Biol Chem. 1988 Aug 15;263(23):11306–11313. [PubMed] [Google Scholar]
  • Neufeld G, Gospodarowicz D. The identification and partial characterization of the fibroblast growth factor receptor of baby hamster kidney cells. J Biol Chem. 1985 Nov 5;260(25):13860–13868. [PubMed] [Google Scholar]
  • Gospodarowicz D, Cheng J. Heparin protects basic and acidic FGF from inactivation. J Cell Physiol. 1986 Sep;128(3):475–484. [PubMed] [Google Scholar]
  • Esch F, Ueno N, Baird A, Hill F, Denoroy L, Ling N, Gospodarowicz D, Guillemin R. Primary structure of bovine brain acidic fibroblast growth factor (FGF). Biochem Biophys Res Commun. 1985 Dec 17;133(2):554–562. [PubMed] [Google Scholar]
  • Schweigerer L, Neufeld G, Friedman J, Abraham JA, Fiddes JC, Gospodarowicz D. Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth. Nature. 1987 Jan 15;325(6101):257–259. [PubMed] [Google Scholar]
  • Vlodavsky I, Folkman J, Sullivan R, Fridman R, Ishai-Michaeli R, Sasse J, Klagsbrun M. Endothelial cell-derived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2292–2296.[PMC free article] [PubMed] [Google Scholar]
  • Sakaguchi M, Kajio T, Kawahara K, Kato K. Antibodies against basic fibroblast growth factor inhibit the autocrine growth of pulmonary artery endothelial cells. FEBS Lett. 1988 Jun 6;233(1):163–166. [PubMed] [Google Scholar]
  • Moscatelli D, Joseph-Silverstein J, Manejias R, Rifkin DB. Mr 25,000 heparin-binding protein from guinea pig brain is a high molecular weight form of basic fibroblast growth factor. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5778–5782.[PMC free article] [PubMed] [Google Scholar]
  • Green N, Alexander H, Olson A, Alexander S, Shinnick TM, Sutcliffe JG, Lerner RA. Immunogenic structure of the influenza virus hemagglutinin. Cell. 1982 Mar;28(3):477–487. [PubMed] [Google Scholar]
  • Baird A, Schubert D, Ling N, Guillemin R. Receptor- and heparin-binding domains of basic fibroblast growth factor. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2324–2328.[PMC free article] [PubMed] [Google Scholar]
  • Folkman J. Tumor angiogenesis. Adv Cancer Res. 1974;19(0):331–358. [PubMed] [Google Scholar]
  • Klagsbrun M, Sasse J, Sullivan R, Smith JA. Human tumor cells synthesize an endothelial cell growth factor that is structurally related to basic fibroblast growth factor. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2448–2452.[PMC free article] [PubMed] [Google Scholar]
  • Masuda Y, Yoshitake Y, Nishikawa K. Secretion of DNA synthesis factor (DSF) by A431 cells that can grow in protein-free medium. Cell Biol Int Rep. 1987 May;11(5):359–365. [PubMed] [Google Scholar]
  • Masuda Y, Yoshitake Y, Nishikawa K. Growth control of A431 cells in protein-free medium: secretory products do not affect cell growth. In Vitro Cell Dev Biol. 1988 Sep;24(9):893–899. [PubMed] [Google Scholar]
Department of Biochemistry, Kanazawa Medical University, Ishikawa, Japan.
Department of Biochemistry, Kanazawa Medical University, Ishikawa, Japan.
Abstract
Two monoclonal antibodies (mAbs) against bovine heparin-binding growth factor II (HBGF-II)/basic fibroblast growth factor (bFGF) were obtained from mouse hybridoma cell lines. They were highly specific for bFGF from bovine, human, and mouse sources and did not cross-react with bovine heparin-binding growth factor I (HBGF-I)/acidic fibroblast growth factor (aFGF). The immunoglobulin class and subclass of these mAbs were IgG1, K. The apparent dissociation constant (Kd) for bFGF of these mAbs ranged from 10(-9) to 10(-10) M. One mAb (bFM-2) also cross-reacted with heat-inactivated bFGF, while the other mAb (bFM-1) did not, suggesting that bFM-1 recognized the conformation of the bFGF molecule necessary for its biological activity. These mAbs inhibited growth of cultured bovine capillary endothelial cells in both the presence and absence of exogenous bFGF, indicating the autocrine action of this growth factor in in vitro growth of these cells. On the other hand, injection of these hybridoma cell lines s.c. into the backs of athymic mice resulted in development of highly vascularized solid tumors and a sustained high level of anti-bFGF activity in the blood of the tumor-bearing mice. These findings suggest that bFGF is not essential as an autocrine or paracrine growth factor for angiogenesis in vivo. These mAbs should be useful in further studies on the physiological role and the conformation-function relationship of bFGF because they block its biological activity.
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