Anti-Müllerian hormone (AMH) autocrine signaling promotes survival and proliferation of ovarian cancer cells

Abstract

In ovarian carcinoma, anti-Müllerian hormone (AMH) type II receptor (AMHRII) and the AMH/AMHRII signaling pathway are potential therapeutic targets. Here, AMH dose-dependent effect on signaling and proliferation was analyzed in four ovarian cancer cell lines, including sex cord stromal/granulosa cell tumors and high grade serous adenocarcinomas (COV434-AMHRII, SKOV3-AMHRII, OVCAR8 and KGN). As previously shown, incubation with exogenous AMH at concentrations above the physiological range (12.5–25 nM) decreased cell viability. Conversely, physiological concentrations of endogenous AMH improved cancer cell viability. Partial AMH depletion by siRNAs was sufficient to reduce cell viability in all four cell lines, by 20% (OVCAR8 cells) to 40% (COV434-AMHRII cells). In the presence of AMH concentrations within the physiological range (5 to 15 pM), the newly developed anti-AMH B10 antibody decreased by 25% (OVCAR8) to 50% (KGN) cell viability at concentrations ranging between 3 and 333 nM. At 70 nM, B10 reduced clonogenic survival by 57.5%, 57.1%, 64.7% and 37.5% in COV434-AMHRII, SKOV3-AMHRII, OVCAR8 and KGN cells, respectively. In the four cell lines, B10 reduced AKT phosphorylation, and increased PARP and caspase 3 cleavage. These results were confirmed in ovarian cancer cells isolated from patients’ ascites, demonstrating the translational potential of these results. Furthermore, B10 reduced COV434-MISRII tumor growth in vivo and significantly enhanced the median survival time compared with vehicle (69 vs 60 days; p = 0.0173). Our data provide evidence for a novel pro-survival autocrine role of AMH in the context of ovarian cancer, which was targeted therapeutically using an anti-AMH antibody to successfully repress tumor growth.

Blood Lead Level as Marker of Increased Risk of Ovarian Cancer in BRCA1 Carriers

“…No direct effect of lead on this signaling pathway has been demonstrated [16]. -Anti-Müllerian hormone (AMH) at physiological concentrations promotes the proliferation and survival of ovarian cancer cells; again, no direct effect of lead on this signaling pathway has been demonstrated [17,18].…”

Stratification of risk based on immune signatures and prediction of the efficacy of immune checkpoint inhibitors in prostate cancer

“…In a study of 1000 patients, the overall risk of prostate cancer has been demonstrated to be correlated with prediagnostic serum AMH levels [29]. Physiological concentrations of endogenous AMH increased the viability of cancer cells [30]. Furthermore, serum amyloid A1 (SAA1) is an inflammatory high-density lipoprotein.…”

Characterization of Immune-Based Molecular Subtypes and Prognostic Model in Prostate Adenocarcinoma

“…A total of four genes, including AMH, PRLR, NOX1, and PGF, are screened as predicators of the prognostic model ( Figure 6 ). Of these, PRLR has been implicated in the pathology of breast and prostate cancer [ 46 , 47 ], NOX1 expression may be increased in prostate cancer with an important role in angiogenesis, cell growth, and tumor pathogenesis [ 48 , 49 ], and both AMH and PGF are reported as crucial genes in tumorigenesis [ 50 , 51 , 52 ]. Based on their potential biological roles and contributions in cancer, the developed immune-related prognostic model is sensitive and effective (AUC = 0.968, and the survival model is an independent prognostic factor), which would provide additional immune-based information for early risk appraisal and treatment management in prostate cancer.…”