VEGF is up-regulated by hypoxic stimulation and related to tumour angiogenesis and severity of disease in oral squamous cell carcinoma: in vitro and in vivo studies

The present study was aimed to speculate whether the up-regulation of VEGF in oral squamous cell carcinoma (OSCC) is associated with oxygen levels, tumor angiogenesis and severity of disease. Under different oxygen levels, VEGF protein production in two oral cancer cell lines was quantitatively documented by using ELISA kit. Correlations between expression of VEGF, microvessel density, and various clinico-pathologic factors were studied in forty patients with OSCC. VEGF production was continuously elevated in supernatants from both cell lines in respond to the drop of oxygen levels. When oxygen level decreased to 1%, there was a 2.1-fold and nearly a 2.9-fold elevation of VEGF production in TSCCa and GNM cell line, respectively. On hypoxia VEGF production also presented a time-dependent up-regulation in both oral cancer cell lines. VEGF positivity was correlated with regional lymph nodal involvement and clinical stage. Microvessel density was significantly higher in VEGF-positive tumors than in VEGF-negative tumors. The presence of hypoxia in oral cancers is partly responsible for the up-regulation of VEGF. The elevation of VEGF expression in OSCC tissues correlates with the increased microvessel density and severity of the disease.