Motility factors identified in supernatants of human cholangiocarcinoma cell lines.

Motility factors, e.g. SF/HGF (scatter factor/hepatocyte growth factor) or AMF (autocrine motility factor) can influence the migration of tumor cells in vitro and may facilitate invasive growth and metastases in vivo. The production of motility factors was studied in cell lines derived from human cholangiocarcinomas. Culture supernatants from 5 different cholangiocarcinoma cell lines (EGI-1, RPMI 7451, MZ CHA-1, MZ CHA-2 and MZ CHA-3) were analyzed in scatter assays with NRK and MDCK cells as indicator cells which react with cellular migration in the presence of motility factors. Culture supernatants from 4 of the 5 cell lines investigated induced migration of the indicator cells thus demonstrating the production of motility factors. Three of the cell lines (MZ CHA-1, MZ CHA-2, RPMI 7451) produced a factor with a molecular weight ranging between 50 and 100 kDa, EGI-1 cells secreted a factor with a molecular weight >100 kDa. None of the factors was identical to HGF as demonstrated by the lacking reactivity in a HGF specific ELISA and by the inability to induce scattering of HPAF indicator cells like HGF. Similar to SF/HGF, the activity of the EGI-1 factor was inhibited by the proteoglycan heparin and stimulated the chemotactic cell migration, but in contrast to SF/HGF it could not induce invasive growth of NRK cells. The production of scatter factors could be involved in tumor progression and formation of metastases of cholangiocarcinomas.