Expression of hypoxia-inducible factor 1alpha in brain tumors: association with angiogenesis, invasion, and progression.

Autor: Zagzag D; Department of Pathology, Division of Neuropathology; Department of Neurosurgery, Microvascular and Molecular Neurooncology Laboratory, Kaplan Cancer Center, New York University Medical Center, New York, New York 10016, USA., Zhong H, Scalzitti JM, Laughner E, Simons JW, Semenza GL
Jazyk: angličtina
Zdroj: Cancer [Cancer] 2000 Jun 01; Vol. 88 (11), pp. 2606-18.
Abstrakt: 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.
(Copyright 2000 American Cancer Society.)
Databáze: MEDLINE
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