DIFFERENTIAL BINDING OF FIBROBLAST GROWTH-FACTOR-2 AND GROWTH-FACTOR-7 TO BASEMENT-MEMBRANE HEPARAN-SULFATE - COMPARISON OF NORMAL AND ABNORMAL HUMAN TISSUES

Fibroblast growth factors (FGFs) play multiple robs during development and in adult tissues as paracrine regulators of growth and differenti ation. FGFs signal through transmembrane receptor tyrosine kinases, bu t heparan sulfate is also required for signaling by members of the FGF family. In addition, heparan sulfate may be involved ill determining tissue distribution of FGFs. Using biotinylated FGF-2 and FGF-7 (KGF) as probes, we have identified specific interactions between FGFs and h eparan sulfates in human tissues. Both FGF species bind to tissue mast cells and to epithelial cell membranes. Binding to basement membrane heparan sulfate is tissue source dependent and specific. Although FGF- 2 strongly binds to basement membrane heparan sulfate in skin and most other tissue sites examined, FGF-7 fails to bind to basement membrane heparan sulfate in most locations. However, its subendothelial matrix in blood vessels and in the basement membrane of a papillary renal ce ll carcinoma, strong FGF-7 binding is seen. In summary, distinct and s pecific affinities of heparan sulfates for different FGFs were identif ied that may affect growth factor activation and local distribution. H eparan sulfate may have a gate-keeper function to either restrict or p ermit diffusion of heparin-binding growth factors across the basement membrane.