The growth of malignant keratinocytes depends on signaling through the PGE(2) receptor EP1

Recent discoveries shed light on the importance of prostaglandin (PG) produ ction in the development of skin cancer. Work by Fischer et al. demonstrate s that skin tumor promotion caused by ultraviolet B radiation can be decrea sed by up to 89% by blocking cyclooxygenase-2 (COX-2) with the drug Celecox ib. A similar study showed that Celecoxib can decrease new tumor formation by 44% in mice that already have tumors. These studies demonstrate the impo rtance of COX-2 and PGs in the development of squamous cell carcinoma. We h ave explored growth signaling in a model of skin tumor progression. Because changes in PG production have been implicated in skin carcinogenesis, we e xamined this pathway. We found that malignant cell lines secrete more prost aglandin E-2 (PGE(2)) than the parental cells. We observed increased expres sion of COX-1 and -2. We also found that these cells express the PGE2 recep tors EP1 and EP4. When the cells are grown in the presence of indomethacin, the growth rate of the malignant cells is decreased. This effect can be re versed by addition of PGE2 or an EP1 agonist to the medium. Thus, we have s hown that skin tumor cells depend in part on PGE2 signaling through the EP1 prostanoid receptor for their in vitro growth.