Inhibition of basic fibroblast growth factor-induced growth promotion by overexpression of syndecan-1.

Abstract

The expression of syndecan-1, the prototype member of the cell surface proteoglycan family, follows morphogenetic rather than histological boundaries during organ formation. As a heparan sulfate-containing cell surface molecule, syndecan-1 can simultaneously bind various components of the extracellular matrix and members of the heparin-binding growth factors. Indeed, syndecan-1 may act as a co-receptor for basic fibroblast growth factor (bFGF) (Salmivirta, M., Heino, J., and Jalkanen, M. (1992) J. Biol. Chem. 267, 17606-17610), allowing the growth factor to bind the tyrosine kinase bFGF receptor. We have studied the role of syndecan-1 in growth factor response by growing 3T3 cells transfected with syndecan-1 in the presence of bFGF. The enhanced expression of syndecan-1 caused down-regulation of bFGF-induced cell proliferation and, at the same time, enhancement of cell matrix interactions. Thus, the induced expression of the heparan sulfate co-receptor (syndecan-1) may provide a mechanism to restrict FGF action and modulate cell-matrix interactions to maintain co-ordinated growth of cells during organ formation.