Expression of hypoxia-inducible factor 1α in brain tumors

Association with angiogenesis, invasion, and progression

David Zagzag, Hua Zhong, Joanne M. Scalzitti, Erik Laughner, Jonathan W. Simons, Gregg L Semenza

Research output: Contribution to journalArticle

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-1α and HIF-1β subunits in human glioma cell lines and brain tumor tissues using Western blot analysis and immunohistochemistry. RESULTS. In glioblastomas multiforme (GBMs), HIF-1α primarily was localized in pseudopalisading cells around areas of necrosis and in tumor cells infiltrating the brain at the tumor margin. In contrast, HIF-1α was expressed in stromal cells throughout hemangioblastomas (HBs). Like HIF-1α, HIF-1β was most highly expressed in high grade tumors but was expressed more widely than HIF-1α, including cells away from necrotic zones. In the brains of mice injected with Glioma 261 cells, a pattern of HIF-1α expression identical to that observed in human GBMs was noted. CONCLUSIONS. In GBMs, the heterogeneous pattern of HIF-1α expression appears to be determined at least in part by tissue oxygenation, whereas in HBs the homogeneous expression of HIF-1α may be driven by an oncogenic rather than a physiologic stimulus. (C) 2000 American Cancer Society.

Original languageEnglish (US)
Pages (from-to)2606-2618
Number of pages13
JournalCancer
Volume88
Issue number11
DOIs
StatePublished - Jun 1 2000

Fingerprint

Hypoxia-Inducible Factor 1
Brain Neoplasms
Glioblastoma
Hemangioblastoma
Glioma
Stromal Cells
Blood Vessels
Neoplasms
Necrosis

Keywords

  • Angiogenesis
  • Glioblastoma multiforme
  • Glioma
  • Hemangioblastoma
  • HIF- 1α
  • HIF-1β
  • Hypoxia

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Expression of hypoxia-inducible factor 1α in brain tumors : Association with angiogenesis, invasion, and progression. / Zagzag, David; Zhong, Hua; Scalzitti, Joanne M.; Laughner, Erik; Simons, Jonathan W.; Semenza, Gregg L.

In: Cancer, Vol. 88, No. 11, 01.06.2000, p. 2606-2618.

Research output: Contribution to journalArticle

Zagzag, David ; Zhong, Hua ; Scalzitti, Joanne M. ; Laughner, Erik ; Simons, Jonathan W. ; Semenza, Gregg L. / Expression of hypoxia-inducible factor 1α in brain tumors : Association with angiogenesis, invasion, and progression. In: Cancer. 2000 ; Vol. 88, No. 11. pp. 2606-2618.
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