Cyclooxygenase-2 pathway correlates with VEGF expression in head and neck cancer. Implications for tumor angiogenesis and metastasis

We evaluated the role of COX-2 pathway in 35 head and neck cancers (HNCs) b y analyzing COX-2 expression and prostaglandin E-2 (PGE(2)) production in r elation to tumor angiogenesis and lymph node metastasis. COX-2 activity was also correlated to vascular endothelial growth factor (VEGF) mRNA and prot ein expression. COX-2 mRNA and protein expression was higher in tumor sampl es than in normal mucosa. PGE(2) levels were higher in the tumor front zone in comparison with tumor core and normal mucosa (P<.0001), Specimens from patients with lymph node metastasis exhibited higher COX-2 protein expressi on (P=.0074), PGE(2) levels (P=.0011) and microvessel density (P<.0001) tha n specimens from patients without metastasis. A significant correlation bet ween COX-2 and tumor vascularization (r(s)=0.450, P=.007) as well as betwee n COX-2 and microvessel density with VEGF expression in tumor tissues was f ound (r(s)=0.450, P=.007; r(s)=0.620, P=.0001, respectively). The induction of COX-2 mRNA and PGE(2) synthesis by EGF and Escherichia coli lipopolysac charide (LPS) in A-431 and SCC-9 cell lines, resulted in an increase in VEG F mRNA and protein production. Indomethacin and celecoxib reversed the EGF- and LPS-dependent COX-2, VEGF, and PGE(2) increases. This study suggests a central role of COX-2 pathway in HNC angiogenesis by modulating VEGF produ ction and indicates that COX-2 inhibitors may be useful in HNC treatment.