Role of M2 muscarinic receptor in epithelial ovarian carcinoma (EOC)

Role of M2 muscarinic receptor in epithelial ovarian carcinoma (EOC) Marilena Taggi1, M. Falcinelli1, V. Cacciamani1, V. Di Paolo1, A. M. Tata2 R. Canipari1 (1) Dipartimento SAIMLAL - Sezione di Istologia –Sapienza, Università di Roma; (2) Dip. Biologia e Biotecnologie Charles Darwin, Sapienza, Università di Roma Epithelial ovarian cancer (EOC) is one of the most common female cancer. EOC arises from the ovarian surface epithelium (OSE) which undergoes a process of injury-repair at each ovulation. In the ovary, a non-neuronal cholinergic system is present, and acetylcholine (ACh) is produced by granulosa cells and luteal cells. We have characterized the expression of muscarinic receptors in two human ovarian carcinoma cell lines (SKOV-3, TOV21-G) and in one immortalized ovarian surface epithelium cell line (i-120). We observed a lower expression of M2 muscarinic receptor subtype in cancer cells, compared to i-120. We investigated its role in the control of cell growth and survival. Treatment with arecaidine propargyl ester hydrobromide (APE), a selective M2 agonist, cell number decreases in a dose and time dependent manner. In the i-120 we observed high levels of cell death, which may be related to the high expression of M2 receptor. Conversely, in cancer cells, there is significantly lower cell death but the APE delays the cell cycle progression. These results suggest that M2 receptor has a negative role on cell growth/vitality, therefore, its downregulation may favor tumor progression.