**2. Effects of HGF on intra-tumor cells during cancer progression**

In the mid-1980s, MET was identified as a mutated oncogene from carcinogen-induced osteosarcoma cells (MNNG-HOS) that transform NIH3T3 fibroblasts (Cooper *et al*., 1984). MET*-*encoding protein has a tyrosine kinase activity (Dean *et al*., 1985), suggesting that MET may be an orphan receptor of growth factors. In the early 1990s, MET-coding product was demonstrated to be a high-affinity receptor for HGF (Bottaro *et al*., 1991; Higuchi *et al*., 1992). Scatter factor (SF) stimulates tumor cell movement, as its name indicates, and is shown molecularly identical to HGF (Konishi *et al*., 1991; Weidner *et al*., 1991). HGF has several activities required for tumor cell invasion and metastasis, as described below. In this section, we summarize the direct effects of HGF on intra-tumor cells, including carcinoma, and on vascular and lymphatic cells prior to discussion of the contribution of HGF-MET cascades during tumor malignancy.
