Smokers produce as much as four times the amount of cyclo-oxygenase-2 (COX-2) in oral mucosal cells lining their mouths as their nonsmoking counterparts do, according an article published in the Jan. 15 issue of the journal Cancer Research.
COX-2 is a cellular protein linked to the development and progression of cancer.
After observing increased COX-2 levels in the oral mucosa of smokers, researchers exposed oral mucosal cells in a culture to tobacco smoke to define the mechanism underlying smoke-induced elevation of COX-2 levels.
They found that tobacco smoke stimulated the oral mucosal cells to rapidly release two proteins—amphiregulin and TGF-alpha—that activate the epidermal growth factor receptor (EGFR), a cell membrane protein associated with various types of cancer. This EGFR activation initiated COX-2 protein production.
"We then were able to block the induction of COX-2 with either a small molecule that inhibited EGFR activity or an antibody that prevented the proteins from binding to and activating the EGFR," said lead author Andrew J. Dannenberg, M.D. "These results strengthen the rationale for targeting not only COX-2, but also EGFR as approaches for reducing the risk of tobacco-related malignancies of the mouth and throat."
