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.
Bibliographical noteFunding Information:
The corresponding author for this work is A. Y. We thank Dougias Noonan and Israel Vlodavsky for most helpful discussions, Tammy Gray and Nathen Aviezer for critical reading of the manuscript, and Tova Shimon and Rosemarie Flick for their excellent technical assistance, This work was supported in part by grants from the Israel Academy of Science, Israel Cancer Research Fund, Minerva Foundation, USA-Israel Binational Science Foundation, the Nationaal Fonds voor Wetenschappelijk Onderzoek of Belgium (grant 3.0073.91), Leven-slijn-1991-Hart en Bloedvaten (grant 7.0043.91), and the Interuniversity Network for Fundamental Research sponsored by the Belgian government. A. Y. is an incumbent of the Alvin and Gertrude Levine Career Development Chair of Cancer Research.