Hepatocyte extracellular matrix modulates expression of growth factors andgrowth factor receptors in human colon cancer cells

We investigated the role of hepatocyte extracellular matrix (ECM) on the gr owth of human colon cancer cell lines. We cultured four cell lines with dif ferent liver-colonizing potential on ECM derived from primary rat hepatocyt e cultures. We investigated the effect of ECM on cell proliferation, clonal growth, and expression of growth factors and growth factor receptors. The highly metastatic cells showed better clonal growth and produced larger col onies on ECM. The proliferation of all colon cancer cell lines was enhanced on hepatocyte ECM, yet inhibited on fibroblast ECM. Screening of autocrine growth factors and receptors showed that the cells expressed growth factor s and receptors of the EGF family: EGF receptor, erb-B2, amphiregulin, and cripto. The expression of cripto mRNA, but not of amphiregulin, was induced in KM12SM cells grown on ECM. All colon cancer cell lines grown on ECM sho wed increased expression of erb-B2. The effect of ECM on erb-B2 expression was mediated by the heparin chains of heparin proteoglycan. ECM from hepato cytes grown in the presence of nitrophenyl-beta-D-xylopyrannoside or sodium chlorate, which prevent formation of heparin proteoglycan, as well as ECM treated with heparinase, had no effect on erb-B2 expression. Our studies su ggest a role for liver ECM as a determinant of colon cancer metastasis. Liv er ECM acts, in part, via induction of members of the EGF family of growth factors and their receptors. (C) 1998 Academic Press.