Expression of Hypoxia-Inducible Factor 1alpha in Brain Tumors: Association With Angiogenesis, Invasion, and Progression

Cancer. 2000 Jun 1;88(11):2606-18.

Abstract

Background: Hypoxia inducible factor-1 (HIF-1) plays a critical role in angiogenesis during vascular development. The authors tested the hypothesis that HIF-1 expression correlates with progression and angiogenesis in brain tumors.

Methods: The authors investigated the expression of the HIF-1alpha and HIF-1beta subunits in human glioma cell lines and brain tumor tissues using Western blot analysis and immunohistochemistry.

Results: In glioblastomas multiforme (GBMs), HIF-1alpha primarily was localized in pseudopalisading cells around areas of necrosis and in tumor cells infiltrating the brain at the tumor margin. In contrast, HIF-1alpha was expressed in stromal cells throughout hemangioblastomas (HBs). Like HIF-1alpha, HIF-1beta was most highly expressed in high grade tumors but was expressed more widely than HIF-1alpha, including cells away from necrotic zones. In the brains of mice injected with Glioma 261 cells, a pattern of HIF-1alpha expression identical to that observed in human GBMs was noted.

Conclusions: In GBMs, the heterogeneous pattern of HIF-1alpha expression appears to be determined at least in part by tissue oxygenation, whereas in HBs the homogeneous expression of HIF-1alpha may be driven by an oncogenic rather than a physiologic stimulus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Neoplasms / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Glioma / metabolism*
  • Hemangioblastoma / metabolism*
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mice
  • Neoplasm Proteins / metabolism*
  • Neovascularization, Pathologic / metabolism*
  • Nuclear Proteins / metabolism*
  • Transcription Factors*
  • Tumor Cells, Cultured

Substances

  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Neoplasm Proteins
  • Nuclear Proteins
  • Transcription Factors