Expression of hypoxia-inducible factor 1alpha in brain tumors: association with angiogenesis, invasion, and progression.
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.
Zagzag
D
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
H
Scalzitti
J M
JM
Laughner
E
E
Simons
J W
JW
Semenza
G L
GL
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism*; D018325:Hemangioblastoma / Q000378:metabolism*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; C497443:Hif1a protein, mouse; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors