ADHESION TO FIBRONECTIN OR COLLAGEN-I GEL INDUCES RAPID, EXTENSIVE, BIOSYNTHETIC ALTERATIONS IN EPITHELIAL-CELLS

Extracellular matrix influences many cellular events. In this study, w e demonstrate that adhesion of human salivary gland (HSG) epithelial c ells to fibronectin-or collagen I gel-coated substrates, mediated by b eta(1) integrins, results in substantial alterations in protein and RN A expression profiles. The large numbers of changes in expression sugg est that simply changing the adhesive substrate has basic effects on t he regulation of cellular biosynthesis. Two-dimensional electrophoresi s of [S-35] methionine-labeled HSG cell proteins identified significan t differences in the patterns of protein expression by cells cultured on nonprecoated substrates, collagen I gels or fibronectin. Thirty-two differentially expressed cDNA clones, which included both novel and p reviously sequenced genes, were up-regulated within 6 hr by culturing HSG cells on fibronectin or collagen I gels. Therefore, adhesion to co llagen I or fibronectin resulted in rapid, widespread changes in cellu lar biosynthetic control. Expression of some genes was induced by liga tion of beta(1) integrins with antifunctional antibodies, whereas the expression of other genes was not induced. Most of the differentially expressed genes were upregulated by adhesion to both fibronectin- and collagen I gel-coated substrates, but a few genes were selectively up- regulated on only one substrate. Furthermore, the up-regulated express ion of some genes was detected within 3 hr, whereas changes in others required 6 hr. Discrete adhesive substrates and integrin molecules dif ferentially affected the expression of a significant number of genes, suggesting that the cellular responses to adhesion were triggered thro ugh several signaling pathways. (C) 1998 Wiley-Liss, Inc.dagger.