In Ovarian Cancer, the Concentration of Anti-Müllerian Hormone Dictates the Choice between Pro-Survival and Pro-Apoptotic Pathways Through Differential ALK2/ALK3 Usage
In ovarian carcinoma, anti-Müllerian hormone (AMH) type II receptor (AMHRII) and the AMH/AMHRII signaling pathway are potential therapeutic targets. Conversely, the role of the three AMH type I receptors (AMHRI; ALK2, ALK3 and ALK6) needs to be clarified. Using four ovarian cancer cell lines and ovarian cancer cells isolated from patients’ tumor ascites, we found that ALK2 and ALK3 are the two main AMHRIs involved in AMH signaling at low and high AMH concentrations, respectively. As expected, high AMH concentrations were associated with apoptosis and decreased clonogenic survival through preferential ALK3 usage. Conversely low AMH concentrations improved cancer cell viability and survival via the ALK2 receptor. Moreover, the AMH siRNA and the anti-AMH antibody B10 inhibited AMH pro-survival effect in vitro and in vivo. These results open the way to an innovative therapeutic approach to suppress AMH proliferative effect, instead of administering high AMH doses to induce cancer cell apoptosis.
Chauvin, Maëva and Garambois, Véronique and Colombo, Pierre-Emmanuel and Chentouf, Myriam and Gros, Laurent and De Brauwere, David-Paul and Robert, Bruno and Mangé, Alain and Jalier, Marta and Dumas, Karen and Martineau, Pierre and Navarro-Teulon, Isabelle and Chardès, Thierry and Pèlegrin, André, In Ovarian Cancer, the Concentration of Anti-Müllerian Hormone Dictates the Choice between Pro-Survival and Pro-Apoptotic Pathways Through Differential ALK2/ALK3 Usage (November 11, 2019). Available at SSRN: https://ssrn.com/abstract=3501841 or http://dx.doi.org/10.2139/ssrn.3501841
This version of the paper has not been formally peer reviewed.
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