EphA3 maintains tumorigenicity and is a therapeutic target in glioblastoma multiforme

Cancer Cell. 2013 Feb 11;23(2):238-48. doi: 10.1016/j.ccr.2013.01.007.

Abstract

Significant endeavor has been applied to identify functional therapeutic targets in glioblastoma (GBM) to halt the growth of this aggressive cancer. We show that the receptor tyrosine kinase EphA3 is frequently overexpressed in GBM and, in particular, in the most aggressive mesenchymal subtype. Importantly, EphA3 is highly expressed on the tumor-initiating cell population in glioma and appears critically involved in maintaining tumor cells in a less differentiated state by modulating mitogen-activated protein kinase signaling. EphA3 knockdown or depletion of EphA3-positive tumor cells reduced tumorigenic potential to a degree comparable to treatment with a therapeutic radiolabelled EphA3-specific monoclonal antibody. These results identify EphA3 as a functional, targetable receptor in GBM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Apoptosis
  • Blotting, Western
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Brain Neoplasms / prevention & control*
  • Cell Differentiation
  • Cell Proliferation
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Glioblastoma / prevention & control*
  • Humans
  • Immunoprecipitation
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mitogen-Activated Protein Kinases / metabolism*
  • Neoplastic Stem Cells / pathology*
  • RNA, Small Interfering / genetics
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, EphA3
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • RNA, Small Interfering
  • EPHA3 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, EphA3
  • Mitogen-Activated Protein Kinases