CD44-Independent Hepatocyte Growth Factor/c-Met Autocrine Loop Promotes Malignant Peripheral Nerve Sheath Tumor Cell Invasion In Vitro

Weiping Su, David H. Gutmann, Arie Perry, Roger Abounader, John Laterra, Larry S. Sherman

Research output: Contribution to journalArticlepeer-review

Abstract

Malignant peripheral nerve sheath tumors (MPNSTs) are invasive peripheral nerve neoplasms that express both the receptor tyrosine kinase c-Met and its ligand hepatocyte growth factor (HGF). The combined expression of these proteins has been implicated in tumor cell growth and metastasis. However, HGF/c-Met autocrine activity requires the presence of a serine protease, the HGF activator (HGFA), and, in some cells, the CD44 transmembrane glycoprotein. Here, we found that HGFA, HGF, c-Met, and CD44 are coexpressed in MPNSTs but their localization did not correlate with increased cell proliferation. The ST8814 MPNST cell line also expresses all of these proteins, can convert pro-HGF to active HGF, and exhibits constitutive c-Met phosphorylation. Blocking c-Met activity or expression inhibits the invasive behavior of these cells but not their proliferation. Interestingly, although a CD44 splice variant contributes to MPNST cell invasion and interacts with c-Met and HGF in ST8814 cells, it is not required for c-Met activation. These data indicate that an HGF/c-Met autocrine loop can promote MPNST invasion through a CD44-independent mechanism and suggest that c-Met, HGFA, and HGF are potential molecular targets to inhibit MPNST metastasis.

Original languageEnglish (US)
Pages (from-to)297-306
Number of pages10
JournalGlia
Volume45
Issue number3
DOIs
StatePublished - Feb 1 2004

Keywords

  • C-Met
  • Hepatocyte growth factor
  • Hepatocyte growth factor activator
  • Invasion
  • Malignant peripheral nerve sheath tumor

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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