Creation of an hepatocyte growth factor/scatter factor autocrine loop in carcinoma cells induces invasive properties associated with increased tumorigenicity.

Exogenous HGF/SF converts subconfluent cultures of NBT-II epithelial carcinoma cells into mobile fibroblast-like cells while being only mitogenic for cells maintained at high density. To investigate the potential role of such factor in tumor progression, we generated HGF/SF-producing NBT-II cells by transfection with an expression plasmid containing human HGF/SF cDNA. HGF/SF-producing cells also exhibit a fibroblastic phenotype. Media conditioned by these cells are potent inducers of in vitro tubulogenesis which can be inhibited with specific anti-HGF/SF antibodies; these antibodies are also able to reverse the scattered phenotype of the HGF/SF-producing cells. In addition spheroids of HGF/SF-producing cells are dispersed into 3D collagen gels suggesting an increase of invasive properties of these cells. When injected in nude mice, these HGF/SF-producing cells induce tumors appearing more rapidly than did those obtained with untransfected cells. These results show that HGF/SF can promote motility and invasive properties of NBT-II bladder carcinoma cells and also confers a tumorigenic advantage when acting as an autocrine factor.