Soluble and matrix-associated heparan sulfate proteoglycans increase expression of erb-B2 and erb-B3 in colon cancer cell lines

We investigated the effect of hepatocyte-derived extracellular matrix (ECM) on the expression of erb-B2 and erb-B3 in colon cancer cell lines, as well as the role of erb-B2 and erb-B3 in colon cancer cell proliferation, Colon cancer cell lines plated on hepatocyte-derived ECM had increased protein l evels of both erb-B2 and erb-B3, The addition of soluble recombinant proteo glycan syndecan-4 also resulted in higher expression of erb-B2 and erb-B3. We prepared hepatocyte-derived ECM from 1 to 7 days' cultures of hepatocyte s, which contained different amounts of sulfated glycosaminoglycans. There was a direct correlation between the amounts of sulfated glycosaminoglycans in the ECM and the levels of erb-B2 and erb-B3 in the colon cell line KM12 . The stimulatory effect of hepatocyte-derived ECM was abolished when the c olon cancer cells were cultured in the presence of antibodies to erb-B2 The se studies show that hepatocyte-derived ECM and the heparan sulfate proteog lycans present in it are responsible for inducing erb-B2 and erb-B3 in colo n cancer cells. The growth stimulatory effect of extracellular matrix is me diated, at least in part, by increased expression of erb-B2. and erb-B3. (C ) 2001 Wiley-Liss. Inc.