Perlecan, basal lamina proteoglycan, promotes basic fibroblast growth factor-receptor binding, mitogenesis, and angiogenesis.
A survey of defined species of cell surface and extracellular matrix heparan sulfate proteoglycans (HSPG) was performed in a search for cellular proteoglycans that can promote bFGF receptor binding and biological activity. Of the various affinity-purified HSPGs tested, perlecan, the large basement membrane HSPG, is found to induce high affinity binding of bFGF both to cells deficient in HS and to soluble FGF receptors. Heparin-dependent mitogenic activity of bFGF is strongly augmented by perlecan. Monoclonal antibodies to perlecan extract the receptor binding promoting activity from active HSPG preparations. In a rabbit ear model for in vivo angiogenesis, perlecan is a potent inducer of bFGF-mediated neovascularization. These results identify perlecan as a major candidate for a bFGF low affinity, accessory receptor and an angiogenic modulator.
Aviezer
D
D
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Hecht
D
D
Safran
M
M
Eisinger
M
M
David
G
G
Yayon
A
A
D000818:Animals; D001485:Basement Membrane / Q000737:chemistry; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004423:Ear / Q000098:blood supply; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000737:chemistry; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011485:Protein Binding; D011509:Proteoglycans / Q000302:isolation & purification / Q000494:pharmacology*; D011817:Rabbits; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*
D016222:Fibroblast Growth Factor 2; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011509:Proteoglycans; D017468:Receptors, Fibroblast Growth Factor; C071927:perlecan