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 ce ll proliferation and expression of growth factors and their receptors in fo ur 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 strongl y metastatic cell lines. Growth inhibition was accompanied by a reduced exp ression of erb-B2 in the colon cells after 4 days in the presence of hepato cytes. In LS174T and LiM6 cells, there was a dramatic reduction in hereguli n-alpha levels in the presence of hepatocytes. Interestingly, after 2 days in culture, hepatocyte-derived soluble factors increased the mRNA levels fo r the EGF family members amphiregulin and cripto. These studies show an inh ibitory effect of hepatocyte-derived soluble factors on the proliferation o f colon cell lines, mediated in part by changes in the expression of autocr ine growth factors and receptors of the EGF and heregulin family. Copyright (C) 2000 S. Karger AG, Basel.