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 (FGFRs) or to cell-surface heparan sulfate proteoglycans (HSPGs).
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 FGFR-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-avb3 antibodies prevent cell adhesion to FGF-2. Also, avb3 of bovine or human origin binds to immobilized FGF-2 in cell-free systems from where it is eluted by a mixture of FGF-2(38-61) plus FGF-2(82-101) fragments.
Finally, anti-avb3 antibody specifically inhibits mitogenesis and plasminogen activator (PA) production induced by free FGF-2 in endothelial cells adherent to tissue culture plastic.
These data demonstrate that FGF-2 interacts with avb3 integrin and that this interaction mediates the capacity of the angiogenic growth factor to induce cell adhesion, mitogenesis, and PA upregulation in endothelial cells.
Molecular Biology of the Cell 1997, 8:2449-2461