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

  • Chapter
Epithelial-Mesenchymal Interactions in Cancer

Part of the book series: Experientia Supplementum ((EXS,volume 74))

Summary

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.

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Authors and Affiliations

  1. ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, P.O. Box B, Frederick, MD, 21702, USA

    J. Cortner, G. F. Vande Woude & S. Rong

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  1. J. Cortner
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  2. G. F. Vande Woude
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  3. S. Rong
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  1. Institute of Oncology, Long Island Jewish Medical Center, New Hyde Park, N.Y., 11042, USA

    I. D. Goldberg  & E. M. Rosen  & 

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© 1995 Birkhäuser Verlag

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Cortner, J., Vande Woude, G.F., Rong, S. (1995). The Met-HGF/SF autocrine signaling mechanism is involved in sarcomagenesis. In: Goldberg, I.D., Rosen, E.M. (eds) Epithelial-Mesenchymal Interactions in Cancer. Experientia Supplementum, vol 74. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-9070-0_6

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  • DOI: https://doi.org/10.1007/978-3-0348-9070-0_6

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-0348-9893-5

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