Correlation Between VEGF and HIF-1alpha Expression in Human Oral Squamous Cell Carcinoma

Understanding the development and progression of oral cancer is critical in the quest for successful therapeutic intervention. The hypoxic microenvironment present in human oral tumor in vivo may actively influence tumor growth and neovascularization. This study correlates expression of both VEGF and HIF-1alpha in normal keratinocytes and oral cancer cell lines and determine whether hypoxia played a role in VEGF and HIF-1alpha regulation. Three human oral cancer cell lines and three normal keratinocytes were exposed to both normoxia and hypoxia culture conditions. Northern and Western blot analysis were used to assess VEGF and HIF-1alpha expression in the different culture conditions. ELISA assays were performed to measure VEGF production in the different cell lines tested. Hypoxia upregulated VEGF and HIF-1alpha expression on both normal and oral cancer cell lines, with a statistically significant difference between normal and oral cancer cell lines. Pattern of hypoxia-induced VEGF mRNA level tightly followed the HIF-1alpha mRNA expression in the cell lines tested. These results suggest that hypoxia regulates both VEGF and HIF-1alpha expression in head and neck carcinoma cell lines, thus establishing a biochemical pathway between tumor hypoxia and neoangiogenesis in these aggressive neoplasms.