Differential binding of fibroblast growth factor-2 and -7 to basement membrane heparan sulfate: comparison of normal and abnormal human tissues.
Fibroblast growth factors (FGFs) play multiple roles during development and in adult tissues as paracrine regulators of growth and differentiation. FGFs signal through transmembrane receptor tyrosine kinases, but heparan sulfate is also required for signaling by members of the FGF family. In addition, heparan sulfate may be involved in determining tissue distribution of FGFs. Using biotinylated FGF-2 and FGF-7 (KGF) as probes, we have identified specific interactions between FGFs and heparan 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, in subendothelial matrix in blood vessels and in the basement membrane of a papillary renal cell carcinoma, strong FGF-7 binding is seen. In summary, distinct and specific affinities of heparan sulfates for different FGFs were identified that may affect growth factor activation and local distribution. Heparan sulfate may have a gatekeeper function to either restrict or permit diffusion of heparin-binding growth factors across the basement membrane.
Friedl
A
A
Department of Pathology, University of Wisconsin-Madison 53792, USA.
Chang
Z
Z
Tierney
A
A
Rapraeger
A C
AC
D016475:3T3 Cells; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011485:Protein Binding; D012867:Skin / Q000378:metabolism / Q000473:pathology
D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances; D006497:Heparan Sulfate; C496453:FGF7 protein, human; C496454:Fgf7 protein, mouse