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