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Expression of hypoxia‐inducible factor 1α in brain tumors
Author(s) -
Zagzag David,
Zhong Hua,
Scalzitti Joanne M.,
Laughner Erik,
Simons Jonathan W.,
Semenza Gregg L.
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20000601)88:11<2606::aid-cncr25>3.0.co;2-w
Subject(s) - angiogenesis , stromal cell , glioma , immunohistochemistry , pathology , human brain , hypoxia inducible factors , hif1a , medicine , cancer research , western blot , hypoxia (environmental) , tumor progression , brain tumor , cancer , biology , gene , chemistry , biochemistry , organic chemistry , psychiatry , oxygen
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. Cancer 2000;88:2606–18. © 2000 American Cancer Society.