Hepatocyte-derived soluble factors regulate proliferation and autocrine growth factor expression in colon cancer cell...

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-alpha 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.