The Met-HGF/SF autocrine signaling mechanism is involved in sarcomagenesis

EXS. 1995;74:89-121. doi: 10.1007/978-3-0348-9070-0_6.

Abstract

Hepatocyte growth factor/scatter factor (HGF/SF) can elicit a wide variety of effects upon cells expressing its receptor, the tyrosine kinase proto-oncogene product Met, including mitogenicity, motility, and morphogenesis. Normally, met expression is restricted to epithelial cells and is activated in a paracrine fashion by HGF/SF secreted from cells of mesenchymal origin. In this chapter, we review data showing that: (i) met over-expression in HGF/SF-expressing NIH/3T3 fibroblasts leads to sarcomagenesis and metastasis via an autocrine mechanism; (ii) Met-HGF/SF autocrine signalling occurs to a low level in normal fibroblasts and to a much greater extent in human sarcomas and sarcoma cell lines; (iii) met expression is enhanced as p53-deficient fibroblasts are passaged in vitro and (iv) met and HGF/SF over-expression are selected for during tumorigenesis of p53-deficient late-passage fibroblasts. Thus, loss of p53 predisposes a mesenchymal cell to over-express met and high level Met-HGF/SF autocrine signaling in mesenchymal cells promotes both sarcomagenesis and metastasis through inappropriate induction of the pleiotropic responses to Met-HGF/SF stimulation.

Publication types

  • Review

MeSH terms

  • 3T3 Cells
  • Animals
  • Gene Expression*
  • Hepatocyte Growth Factor / biosynthesis
  • Hepatocyte Growth Factor / physiology*
  • Humans
  • Mice
  • Proto-Oncogene Proteins c-met
  • Proto-Oncogenes
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor Protein-Tyrosine Kinases / physiology
  • Sarcoma / pathology*
  • Sarcoma / physiopathology*
  • Sarcoma, Experimental / pathology
  • Sarcoma, Experimental / physiopathology
  • Signal Transduction*
  • Tumor Cells, Cultured

Substances

  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases