MURINE MODELS OF LIVER METASTASIS

Even though the liver is a relevant metastatic site for several human malignant tumors, mechanisms of organ-specific metastasis to the liver remain largely unknown. In the following paper we summarize the resul ts obtained with different murine model systems which have been set up to elucidate the above mechanisms, and describe our own results with two murine models: the F9 teratocarcinoma and the B16 melanoma. While the F9 teratocarcinoma model system underscores the roles of both adhe sion and growth stimulation in the target organ, the B16 melanoma mode l strengthens the relevance of paracrine growth stimulation. Moreover, B16 melanoma cells selected in vivo for increased liver colonization ability appear to depend on cell-to-cell contact with hepatocytes in o rder to gain efficient growth stimulation. When we next tried to ident ify the molecule(s) responsible for the growth effect in a liver plasm a membrane extract, we found that such activity was mediated by two cl osely related protein bands. These turned out to be two different form s of transferrin (Tf), one of which is specifically present on the hep atocyte surface. Moreover, when we analyzed the different B16 lines fo r the expression of c-Met [the receptor for the hepatocyte growth fact or-scatter factor (HGF/SF)], we found that liver-specific LS9 had more of this protein than lung-specific F10 or parental F1, suggesting a r ole for HGF/SF in liver colonization by B16 melanoma cells.