Abstract: In ovarian carcinoma, Müllerian Inhibiting Substance (MIS) type II receptor (MISRII) and the MIS/MISRII signaling pathway are potential therapeutic targets. Conversely, the role of the three MIS type I receptors (MISRI; ALK2, ALK3 and ALK6) in this cancer needs to be clarified. Using four ovarian cancer cell lines and ovarian cancer cells isolated from patients' tumor ascites, the inventors found that ALK2 and ALK3 are the two main MISRIs involved in MIS signaling at low and high MIS concentrations, respectively. Moreover, high MIS concentrations were associated with apoptosis and decreased clonogenic survival, whereas low MIS concentrations improved cancer cell viability. Finally, the inventors showed that anti-MIS antibody B10 inhibited MIS pro-survival effect. These last results open the way to an innovative therapeutic approach to suppress MIS proliferative effect, instead of administering high doses of MIS to induce cancer cell apoptosis.

Abstract: In ovarian carcinoma, Müllerian Inhibiting Substance (MIS) type II receptor (MISRII) and the MIS/MISRII signaling pathway are potential therapeutic targets. Conversely, the role of the three MIS type I receptors (MISRI; ALK2, ALK3 and ALK6) in this cancer needs to be clarified. Using four ovarian cancer cell lines and ovarian cancer cells isolated from patients' tumor ascites, the inventors found that ALK2 and ALK3 are the two main MISRIs involved in MIS signaling at low and high MIS concentrations, respectively. Moreover, high MIS concentrations were associated with apoptosis and decreased clonogenic survival, whereas low MIS concentrations improved cancer cell viability. Finally, the inventors showed that MIS siRNA inhibited MIS pro-survival effect. These last results open the way to an innovative therapeutic approach to suppress MIS proliferative effect, instead of administering high doses of MIS to induce cancer cell apoptosis.