Hepatocyte-derived soluble factors regulate proliferation and autocrine growth factor expression in colon cancer cell lines of varying liver- colonizing capability

We investigated the role of hepatocyte-derived soluble growth factors on cell proliferation and expression of growth factors and their receptors in four colon cancer cell lines of varying liver-colonizing ability. Cocultures of hepatocytes and colon cells and cultures of colon cells with hepatocyte- conditioned medium resulted in growth inhibition of both weakly and strongly metastatic cell lines. Growth inhibition was accompanied by a reduced expression of erb-B2 in the colon cells after 4 days in the presence of hepatocytes. In LS174T and LiM6 cells, there was a dramatic reduction in heregulin-α levels in the presence of hepatocytes. Interestingly, after 2 days in culture, hepatocyte-derived soluble factors increased the mRNA levels for the EGF family members amphiregulin and cripto. These studies show an inhibitory effect of hepatocyte-derived soluble factors on the proliferation of colon cell lines, mediated in part by changes in the expression of autocrine growth factors and receptors of the EGF and heregulin family. Copyright (C) 2000 S. Karger AG, Basel.