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

Oncogene. 1994 Apr;9(4):1091-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibody Specificity
  • Cell Adhesion / drug effects
  • Cell Division / drug effects
  • Culture Media, Conditioned / pharmacology
  • Female
  • Fibroblasts / pathology
  • Hepatocyte Growth Factor / pharmacology*
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasms, Experimental / etiology
  • Rats
  • Transfection
  • Tumor Cells, Cultured
  • Urinary Bladder Neoplasms / pathology*


  • Culture Media, Conditioned
  • Hepatocyte Growth Factor