The Met/ HGF receptor is over-expressed in human osteosarcomas and is activated by either a paracrine or an autocrine circuit

Riccardo Ferracini, Maria Flavia Di Renzo, Katia Scotlandi, Nicola Baldini, Martina Olivero, PierLuigi Lollini, Ottavio Cremona, Mario Campanacci, Paolo Maria Comoglio

Research output: Contribution to journalArticlepeer-review

Abstract

The c-MET oncogene encodes the receptor for the Hepatocyte Growth Factor/Scatter Factor (HGF), a cytokine that stimulates the invasive growth of normal and neoplastic cells. The Met/HGF receptor is expressed by epithelial cells and its ligand by cells of mesenchymal origin. Receptor-ligand interaction occurs via a paracrine circuit. We studied the expression of the Met/HGF receptor and of its ligand in mesenchymal human tumours by examining 39 clinical samples of bone tumours. The Met/HGF receptor was not detectable in the majority of bone tumours, as expected from their mesenchymal origin. Notably, the receptor was overexpressed in 60% of the osteosarcomas examined. In 12 osteosarcoma cell lines the Met/HGF receptor was overexpressed, phosphorylated by HGF stimulation and fully functional. HGF was detected in two out of seven clinical specimens of osteosarcoma. The ligand and the receptor are co-expressed in two clonal osteosarcoma cell lines. In these lines the Met/HGF receptor was constitutively phosphorylated; phosphorylation was suppressed by suramin treatment, a known blocker of autocrine loops. These data suggest that activation of the Met/HGF receptor by a paracrine or an autocrine mechanism might play a role in the particularly aggressive behaviour of osteosarcomas.

Original languageEnglish
Pages (from-to)739-749
Number of pages11
JournalOncogene
Volume10
Issue number4
Publication statusPublished - Feb 16 1995

Keywords

  • Growth factors
  • Osteosarcoma
  • Tyrosine kinase receptor

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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