title: alphavbeta3 integrin mediates the cell-adhesive capacity and biological activity of basic fibroblast growth factor (FGF-2) in cultured endothelial cells.
abstract: Fibroblast growth factor-2 (FGF-2) immobilized on non-tissue culture plastic promotes adhesion and spreading of bovine and human endothelial cells that are inhibited by anti-FGF-2 antibody. Heat-inactivated FGF-2 retains its cell-adhesive activity despite its incapacity to bind to tyrosine-kinase FGF receptors or to cell-surface heparan sulfate proteoglycans. Recombinant glutathione-S-transferase-FGF-2 chimeras and synthetic FGF-2 fragments identify two cell-adhesive domains in FGF-2 corresponding to amino acid sequences 38-61 and 82-101. Both regions are distinct from the FGF-receptor-binding domain of FGF-2 and contain a DGR sequence that is the inverse of the RGD cell-recognition sequence. Calcium deprivation, RGD-containing eptapeptides, soluble vitronectin (VN), but not fibronectin (FN), inhibit cell adhesion to FGF-2. Conversely, soluble FGF-2 prevents cell adhesion to VN but not FN, thus implicating VN receptor in the cell-adhesive activity of FGF-2. Accordingly, monoclonal and polyclonal anti-alphavbeta3 antibodies prevent cell adhesion to FGF-2. Also, purified human alphavbeta3 binds to immobilized FGF-2 in a cation-dependent manner, and this interaction is competed by soluble VN but not by soluble FN. Finally, anti-alphavbeta3 monoclonal and polyclonal antibodies specifically inhibit mitogenesis and urokinase-type plasminogen activator (uPA) up-regulation induced by free FGF-2 in endothelial cells adherent to tissue culture plastic. These data demonstrate that FGF-2 interacts with alphavbeta3 integrin and that this interaction mediates the capacity of the angiogenic growth factor to induce cell adhesion, mitogenesis, and uPA up-regulation in endothelial cells.
authors.affiliation: Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rusnati
authors.forename: E
authors.initials: E
authors.lastname: Tanghetti
authors.forename: P
authors.initials: P
authors.lastname: Dell'Era
authors.forename: A
authors.initials: A
authors.lastname: Gualandris
authors.forename: M
authors.initials: M
authors.lastname: Presta
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008934:Mitogens / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010969:Plastics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017384:Sequence Deletion / Q000235:genetics; D012995:Solubility; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000906:Antibodies; D005353:Fibronectins; D008934:Mitogens; D009842:Oligopeptides; D010969:Plastics; D019030:Receptors, Vitronectin; D011993:Recombinant Fusion Proteins; D019096:Vitronectin; D016222:Fibroblast Growth Factor 2; C047981:arginyl-glycyl-aspartic acid; D006493:Heparin; D014568:Urokinase-Type Plasminogen Activator; D002118:Calcium