Inhibitory effects of HGF antagonist on invasion/metastasis of tumor cells.

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Invasion and metastasis of tumor cells follows their interaction with stromal cells. Hepatocyte growth factor (HGF) is a mesenchymal- or stromal-derived mediator that affects the growth and the invasiveness of tumor cells. We prepared an antagonistic molecule, designated as HGF/NK4, from partially digested recombinant HGF.HGF/NK4 competitively inhibited the HGF binding to its receptor c-Met, and abrogated the mitogenic, motpgenic, and morphogenic actions of HGF.In addition, HGF/NK4 almost completely suppressed HGF-induced scattering and invasion of tumor cells in vitro. Furthermore, HGF/NK4 drastically inihibited growth, invasion, and metastasis of tumor cells subcutaneously implanted into nude mouse. These results suggest that there is a unique therapeutic potential for HGF/NK4 to prevent tumor invasion and metastasis.