HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR STIMULATES CHEMOTAXIS AND GROWTH OF MALIGNANT MESOTHELIOMA CELLS THROUGH C-MET RECEPTOR

Hepatocyte growth factor (HGF) and its receptor c-met are present in s everal human tissues but their expression in mesothelial cells has not been examined. In this study, we have investigated the expression of HGF and c-met in normal human mesothelial cells and 11 human malignant mesothelioma cell lines. Using RT-PCR and Western blotting we found t hat HGF is produced by 3/11 mesothelioma cell lines whereas c-met is e xpressed in 11/11 mesothelioma cell lines. In addition, c-met expressi on was also found in 6/6 cell samples obtained from pleural fluids of patients with mesothelioma. In contrast, neither normal cultured mesot helial cells nor mesothelial cells obtained directly from patients wit hout mesothelioma expressed HGF nor c-met. We have also analysed the b iological function of HGF and c-met in mesothelioma cell lines. Recomb inant human (rh) HGF stimulated both directional (chemotactic) and ran dom (chemokinetic) motility in all mesothelioma cell lines tested. Fur thermore, mesothelioma serum free conditioned medium containing HGF st imulated mesothelioma cell migration. This effect could be blocked in the presence of neutralizing anti-HGF monoclonal antibodies (MAbs) in the assay. Addition of HGF to mesothelioma cells cultured on collagen type IV was associated with induction of bipolar shape and protrusion of prominent pseudopodia. We have also found that rhHGF was mitogenic for mesothelioma cells. Our findings suggest that expression of HGF/c- met is involved not only in mesothelioma progression but also in its g rowth and migration and that c-met expression found in mesothelioma ce lls taken directly from patients may be of diagnostic importance. (C) 1998 Wiley-Liss, Inc.