ESTABLISHMENT OF A HEPATOCYTE CELL-LINE PRODUCING GROWTH-PROMOTING FACTORS FOR LIVER-COLONIZING TUMOR-CELLS

A hepatocyte derived cell line designated MLE-15A2 was established fro m a primary culture of mouse hepatocytes, The MLE-15A2 cells appeared to retain the basic nature of hepatocytes in that they showed morpholo gy of an epithelial cell type and secreted albumin into the culture me dium, These cells were grown on collagen-coated plates and could be ea sily expanded to a large-scale culture, Therefore, MLE-15A2 cells may provide a more useful model for studying liver microenvironments than primary cultures of hepatocytes. We found that conditioned media from MLE-15A2 cells, as well as from primary cultures of hepatocytes, promo ted the proliferation of highly liver-colonizing colon 26 NL-17 cells better than the poorly liver-colonizing colon 26 NL-4 cells, Moreover, the conditioned media stimulated the growth of some human colon cance r cell lines, These results indicate that MLE-15A2 cells secrete growt h factors that selectively stimulate certain tumor cell types, Hepatoc yte-derived growth factors may regulate selective survival and coloniz ation of tumor cells in the process of liver metastasis. The growth-pr omoting activity was unaffected by dialysis, was stable at 80 degrees C for 30 min and was bound to a heparin-Sepharose column, The major ac tivity was eluted from the column with 0.7-0.75 M NaCl, and some minor activities eluted with lower concentrations of NaCl, These results su ggest that the active components are heterogeneous heparin-binding pro teins with lower affinity to heparin than platelet-derived and fibrobl ast growth factors.