IGFBP2 promotes glioma tumor stem cell expansion and survival

David Hsieh, Antony Hsieh, Baldassarre Stea, Ron Ellsworth

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

IGFBP2 is overexpressed in the most common brain tumor, glioblastoma (GBM), and its expression is inversely correlated to GBM patient survival. Previous reports have demonstrated a role for IGFBP2 in glioma cell invasion and astrocytoma development. However, the function of IGFBP2 in the restricted, selfrenewing, and tumorigenic GBM cell population comprised of tumor-initiating stem cells has yet to be determined. Herein we demonstrate that IGFBP2 is overexpressed within the stem cell compartment of GBMs and is integral for the clonal expansion and proliferative properties of glioma stem cells (GSCs). In addition, IGFBP2 inhibition reduced Akt-dependent GSC genotoxic and drug resistance. These results suggest that IGFBP2 is a selective malignant factor that may contribute significantly to GBM pathogenesis by enriching for GSCs and mediating their survival. Given the current dearth of selective molecular targets against GSCs, we anticipate our results to be of high therapeutic relevance in combating the rapid and lethal course of GBM.

Original languageEnglish (US)
Pages (from-to)367-372
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume397
Issue number2
DOIs
StatePublished - Jun 25 2010
Externally publishedYes

Keywords

  • Glioblastoma
  • IGF
  • IGFBP2
  • Tumor stem cell

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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