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

BACKGROUND, Hypoxia inducible factor-1 (HIF-1) plays a critical role in ang iogenesis during vascular development. The authors tested the hypothesis th at HIF-1 expression correlates with progression and angiogenesis in brain t umors. 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 W estern blot analysis and immunohistochemistry. RESULTS. In glioblastomas multiforme (GBMs), HIF-1 alpha primarily was loca lized in pseudopalisading cells around areas of necrosis and in tumor cells infiltrating the brain at the tumor margin. In contrast, HIF-1 alpha was e xpressed in stromal cells throughout hemangioblastomas (HBs). Like HIF-1 al pha, HIF-1 beta was most highly expressed in high grade tumors but was expr essed more widely than HIF-1 alpha, including cells away from necrotic zone s. 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 oncogeni c rather than a physiologic stimulus. (C) 2000 American Cancer Society.