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 language | English (US) |
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Pages (from-to) | 2606-2618 |
Number of pages | 13 |
Journal | Cancer |
Volume | 88 |
Issue number | 11 |
DOIs | |
State | Published - Jun 1 2000 |
Keywords
- Angiogenesis
- Glioblastoma multiforme
- Glioma
- HIF- 1α
- HIF-1β
- Hemangioblastoma
- Hypoxia
ASJC Scopus subject areas
- Oncology
- Cancer Research