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JMG, Female, Humans, Animals, Mice, Anti-Mullerian Hormone, Ovarian Neoplasms, Peptide Hormones, Mice, Transgenic, Receptors, Transforming Growth Factor beta, Tumor Microenvironment

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Cell Rep. 2023;42(7):112730.







This work was supported by the Assistant Secretary of Defense for Health Affairs through the Ovarian Cancer Research Program under award no. W81XWH-171-0212. The US Army Medical Research Acquisition Activ- ity, 820 Chandler Street, Fort Detrick, MD 21702-5014 is the awarding and administering acquisition office. This work was supported by the central focus of the Dana-Farber/Harvard Cancer Center (DF/HCC) SPORE in Ovarian Cancer. This work was also supported by the Massachusetts Gen- eral Hospital Department of Surgery Patricia K. Donahoe, MD, Surgeon- Scientist Research Program: Mid-Career Catalyst Award.


Cancer-associated mesothelial cells (CAMCs) in the tumor microenvironment are thought to promote growth and immune evasion. We find that, in mouse and human ovarian tumors, cancer cells express anti-Mullerian hormone (AMH) while CAMCs express its receptor AMHR2, suggesting a paracrine axis. Factors secreted by cancer cells induce AMHR2 expression during their reprogramming into CAMCs in mouse and human in vitro models. Overexpression of AMHR2 in the Met5a mesothelial cell line is sufficient to induce expression of immunosuppressive cytokines and growth factors that stimulate ovarian cancer cell growth in an AMH- dependent way. Finally, syngeneic cancer cells implanted in transgenic mice with Amhr2 CAMCs grow significantly slower than in wild-type hosts. The cytokine profile of Amhr2 tumor-bearing mice is altered and their tumors express less immune checkpoint markers programmed-cell-death 1 (PD1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4). Taken together, these data suggest that the AMH AMHR2 axis plays a critical role in regulating the pro-tumoral function of CAMCs in ovarian cancer.


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