Retrogenic expression of the MET proto-oncogene correlates with the invasive phenotype of human rhabdomyosarcomas

Riccardo Ferracini, Martina Olivero, Maria Flavia Di Renzo, Marina Martano, Carla De Giovanni, Patrizia Nanni, Giuseppe Basso, Katia Scotlandi, Pier Luigi Lollini, Paolo M. Comoglio

Research output: Contribution to journalArticlepeer-review

Abstract

The MET oncogene encodes the receptor for HGF/ Scatter Factor, known to control cell motility and invasion in epithelial cells. We report that the Met/HGF receptor, absent in differentiated adult skeletal muscles, is aberrantly expressed in clinical samples and in established cell lines of human rhabdomyosarcomas. In both the embryonal and alveolar histotypes the oncogene is overexpressed and, in some cases, amplified. The Met receptor is exposed at the cell surface and is functionally active in response to HGF/Scatter Factor. Accordingly, rhabdomyosarcoma cells exhibit an invasive phenotype in vitro in response to exogenous HGF/Scatter factor. As the factor is known to be produced by connective tissues, a paracrine stimulation of rhabdomyosarcoma invasiveness in vivo is hypothesized. Two alveolar rhabdomyosarcomas were found to co-express the 'two-kringle' alternatively-spliced HGF/Scatter Factor variant, which has been previously shown to stimulate cell motility and matrix invasion in vitro. These cells displayed the invasive phenotype in the absence of exogenous HGF/Scatter Factor, suggesting an autocrine mechanism in vivo. These data indicate that aberrant expression of the provides rhabdomyosarcoma cells with the same property as embryonal myoblasts to migrate into the surrounding connective tissues.

Original languageEnglish
Pages (from-to)1697-1705
Number of pages9
JournalOncogene
Volume12
Issue number8
Publication statusPublished - 1996

Keywords

  • Hepatocyte growth factor
  • Proto-oncogenes
  • Rhabdomyosarcoma
  • Tyrosine kinase receptors

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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