Correlation of expression of cyclooxygenase-2, vascular endothelial growth factor, and peroxisome proliferator-activated receptor δ with head and neck squamous cell carcinoma

Cyclooxygenase (COX) is the rate-limiting enzyme in the formation of prostaglandins from arachidonic acid. COX exists in 2 isoforms, COX-1 and COX-2. These isoforms are encoded by separate genes and demonstrate cell-specific expression and regulation. Peroxisome proliferator-activated receptor delta (PPAR delta) is a nuclear transcription factor that is activated by prostacyclin. Vascular endothelial growth factor (VEGF) is a proangiogenic factor that is up-regulated in various tumors. Vascular endothelial growth factor has been shown to interact with COX-derived prostaglandins in angiogenesis. To better understand the roles of these genes in head and neck squamous cell carcinoma (HNSCCA), we examined the differential expression of the COX1, COX2, VEGF, and PPAR delta genes in these tumors. Tissue samples from patients with HNSCCA were analyzed for COX-1, COX-2, VEGF, and PPAR delta messenger RNAs (mRNAs) by in situ hybridization. COX-1 and COX-2 mRNAs were also evaluated with Northern blot hybridization. Immunohistochemistry was used to analyze for COX-2 and PPAR delta proteins. Results showed focal areas of accumulation for COX-2, VEGF, and PPAR delta but not COX-1 in human HNSCCA. Northern blot hybridization showed higher levels of COX-2 mRNA in HNSCCA than in normal tissue. This suggests a supportive role of COX-2 in development and/or progression of HNSCCA. In addition, PPAR delta may be a receptor for COX-2-produced prostaglandins in HNSCCA. There is a potential role for selective COX-2 inhibitors in the treatment of these lesions.