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Published on: December 9, 2016

RON receptor tyrosine kinase in human gliomas: expression, function, and identification of a novel soluble splice

Carmen Eckerich1, Alexander Schulte, Tobias Martens

  • 1Department of Neurosurgery, Laboratory for Brain Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse, Hamburg, Germany.

Journal of Neurochemistry
|June 13, 2009
PubMed

Insights

A novel soluble receptor variant, RONDelta90, inhibits malignant glioma cell migration. This discovery offers potential therapeutic targets for glioblastoma (GBM) by modulating the receptor tyrosine kinase RON signaling pathway.

Area of Science:

  • Neuro-oncology
  • Molecular biology
  • Cancer research

Background:

  • Malignant gliomas, including glioblastoma (GBM), are aggressive brain tumors characterized by diffuse infiltration.
  • The receptor tyrosine kinase RON (recepteur d'origine nantais) and its ligand MSP (macrophage-stimulating protein) are implicated in cancer progression.
  • Aberrant expression of RON splice variants with oncogenic activity has been observed in GBM.

Purpose of the Study:

  • To investigate the role of RON signaling in malignant gliomas.
  • To identify and characterize novel RON splice variants in GBM.
  • To evaluate the functional impact of these variants on glioma cell behavior.

Main Methods:

  • Analysis of RON splice variant expression in human glioma tissues and cell lines.
  • Cloning and expression of the novel RONDelta90 variant.
  • Biochemical assays to assess RON phosphorylation and cell-based assays for migration and motility.
  • Purification and functional characterization of recombinant RONDelta90 protein.

Main Results:

  • Several oncogenic RON splice variants are expressed in GBM.
  • A novel soluble splice variant, RONDelta90, lacking exon 6, was identified.
  • RONDelta90 inhibits MSP-induced RON phosphorylation and attenuates glioma cell migration and motility.
  • RONDelta90 transcripts are found in normal brain and low-grade astrocytomas, but variably in high-grade astrocytomas.

Conclusions:

  • RONDelta90 is a novel soluble antagonistic variant of the RON receptor.
  • This variant may act as a physiological modulator of RON signaling.
  • Oncogenic RON splice variants in malignant gliomas represent potential therapeutic targets for inhibiting RON activity.

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