Exploring the regulatory role of isocitrate dehydrogenase mutant protein on glioma stem cell proliferation

Eur Rev Med Pharmacol Sci. 2016 Aug;20(16):3378-84.

Abstract

Objective: Glioma is the most lethal form of cancer that originates mostly from the brain and less frequently from the spine. Glioma is characterized by abnormal regulation of glial cell differentiation. The severity of the glioma was found to be relaxed in isocitrate dehydrogenase 1 (IDH1) mutant. The present study focused on histological discrimination and regulation of cancer stem cell between IDH1 mutant and in non-IDH1 mutant glioma tissue.

Patients and methods: Histology, immunohistochemistry and Western blotting techniques are used to analyze the glioma nature and variation in glioma stem cells that differ between IDH1 mutant and in non-IDH1 mutant glioma tissue.

Results: The aggressive form of non-IDH1 mutant glioma shows abnormal cellular histological variation with prominent larger nucleus along with abnormal clustering of cells. The longer survival form of IDH1 mutant glioma has a control over glioma stem cell proliferation. Immunohistochemistry with stem cell markers, CD133 and EGFRvIII are used to demonstrate that the IDH1 mutant glioma shows limited dependence on cancer stem cells and it shows marked apoptotic signals in TUNEL assay to regulate abnormal cells. The non-IDH1 mutant glioma failed to regulate misbehaving cells and it promotes cancer stem cell proliferation.

Conclusions: Our finding supports that the IDH1 mutant glioma has a regulatory role in glioma stem cells and their survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms
  • Cell Proliferation
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Isocitrate Dehydrogenase*
  • Mutant Proteins
  • Mutation
  • Neoplastic Stem Cells

Substances

  • Mutant Proteins
  • Isocitrate Dehydrogenase
  • IDH1 protein, human