Importance of the EP1 receptor in cutaneous UVB-induced inflammation and tumor development

Chronic exposure to UV light, the primary cause of skin cancer, results in the induction of high levels of cyclooxygenase-2 (COX-2) expression in the skin. The involvement of COX-2 in the carcinogenesis process is mediated by its enzymatic product, prostaglandin E-2 (PGE(2)). PGE2 has been shown to have a variety of activities that can contribute to tumor development and growth. The effects of PGE2 on different cell types are mediated by four E prostanoid (EP) receptors, EP1-EP4. While recent studies have demonstrated the importance of EP1 in the development of colon and breast cancer, the extent of EP1 involvement in the cutaneous photocarcinogenesis process is unknown. This study found that topical treatment with celecoxib or the specific EP1 antagonist ONO-8713 decreased acute UVB-induced inflammation in the skin and significantly reduced the number of tumors per mouse following 25 weeks of UVB exposure and topical treatment. This study suggests that drugs designed to block EP1 may have the potential to be used as anti-inflammatory and/or chemopreventive agents that reduce the risk of skin cancer development.