Amphiregulin as a tumor promoter for oral squamous cell carcinoma: Involvement of cyclooxygenase 2

Amphiregulin (AR), an epidermal growth factor (EGF)-like molecule, is a mitogen for keratinocytes. Squamous cell carcinoma (SCC) is a tumor derived from keratinoctyes. Expression of AR mRNA positively correlated with the clinical progression of 39 oral SCC. Oral SCC line, KB, was used as a model to study if increased expression of AR altered the biological behaviors of SCC cells. Exogenous AR dose-dependently enhanced the proliferation of KB cells expressing EGF receptor 1 (EGFR-1), a major receptor for AR, but little AR. Neutralizing anti-AR antibody significantly reversed the stimulatory effect of exogenous AR on KB cell proliferation. Ectopically expressed AR in stable clones manifested higher abilities to proliferate, migrate and invade Matrigel than vector control. Cyclooxygenase 2 (COX-2), but not metalloprotease 9 (MMP-9) mRNA, was increased in all the AR-expressing stable clones. In summary, AR behaves as a tumor promoter for oral SCC cells partly via increased expression of COX-2.