The Expression of Anti-Müllerian Hormone Type II Receptor (AMHRII) in Non-Gynecological Solid Tumors Offers Potential for Broad Therapeutic Intervention in Cancer

Abstract

The anti-Müllerian hormone (AMH) belongs to the TGF-β family and plays a key role during fetal sexual development. Various reports have described the expression of AMH type II receptor (AMHRII) in human gynecological cancers including ovarian tumors. According to qRT-PCR results confirmed by specific In-Situ Hybridization (ISH) experiments, AMHRII mRNA is expressed in an extremely restricted number of normal tissues. By performing ISH on tissue microarray of solid tumor samples AMHRII mRNA was unexpectedly detected in several non-gynecological primary cancers including lung, breast, head and neck, and colorectal cancers. AMHRII protein expression, evaluated by immunohistochemistry (IHC) was detected in approximately 70% of epithelial ovarian cancers. Using the same IHC protocol on more than 900 frozen samples covering 18 different cancer types we detected AMHRII expression in more than 50% of hepato-carcinomas, colorectal, lung, and renal cancer samples. AMHRII expression was not observed in neuroendocrine lung tumor samples nor in non-Hodgkin lymphoma samples. Complementary analyses by immunofluorescence and flow cytometry confirmed the detection of AMHRII on a panel of ovarian and colorectal cancers displaying comparable expression levels with mean values of 39,000 and 50,000 AMHRII receptors per cell, respectively. Overall, our results suggest that this embryonic receptor could be a suitable target for treating AMHRII-expressing tumors with an anti-AMHRII selective agent such as murlentamab, also named 3C23K or GM102. This potential therapeutic intervention was confirmed in vivo by showing antitumor activity of murlentamab against AMHRII-expressing colorectal cancer and hepatocarcinoma Patient-Derived tumor Xenografts (PDX) models.

Anti-Müllerian hormone: a novel biomarker for aggressive prostate cancer? Emerging evidence from a prospective study of radical prostatectomies

“…More speci cally, there is evidence that AMH exerts apoptotic action in prostatic cancer cell lines in vitro (20)(21)(22). AMH acts by binding to its receptor, and AMH receptor II has been found to be overexpressed in prostate cancer cells (34,35). Thus, AMH might also induce apoptosis in prostate cancer in vivo.…”

The roles of anti-Müllerian hormone in breast cancer

“…Interestingly, AMHRII traces have been found in several extragonadal organs, such as lung, pituitary, hypothalamus, and motor nerves ( Garrel et al 2016 , Barbotin et al 2019 , Barret et al 2021 , Silva & Giacobini 2021 ), indicating that AMHRII is not only expressed in cells of gonad-related organs, including testicular Sertoli and interstitial cells, ovarian membrane and granulosa cells, prostate, endometrium, and breast ductal epithelium ( Segev et al 2001 , 2002 , Wang et al 2009 , Pfennig et al 2015 ). This suggests that AMH may have more roles in addition to the already elucidated reproductive functions.…”

“…Of all chemotherapeutic drugs, alkylating agents are the most toxic to ovaries, among which cyclophosphamide (CTX) is widely used in the treatment of a variety of malignant tumors and autoimmune diseases, and it is also the basic ingredient of first-line chemotherapy for breast cancer ( Jiang et al 2013 ). CTX can directly damage the DNA of all levels of follicles ( Barret et al 2021 ). It has also been noted that granulosa cells of growing follicles, which can produce and secrete AMH, are particularly sensitive to alkylating agents ( Yeh et al 2009 , Horicks et al 2015 , Lambertini et al 2019 ).…”

Anti-Müllerian Hormone and Polycystic Ovary Syndrome in Women and Its Male Equivalent

“…In males, AMHR2 is expressed by mesenchymal cell of the Müllerian ducts, Sertoli, Leydig (reviewed in [ 25 ]), and germ cells of the testes [ 30 ], but also in the prostate [ 31 ]. In addition, AMHR2 has been detected in the lungs [ 32 ], the motoneurons [ 26 ], the neurons [ 27 ], the hypothalamus [ 28 ], the gonadotrope cells of the pituitary gland [ 29 ], the pancreas [ 33 ], and the adrenals [ 33 ].…”