Localization of Mullerian inhibiting substance receptors in various human cancer cell lines

Rodina, A. V.; Gukasova, N. V.; Makarov, Vladimir; Кондрашева, И.Г.; Khomyakova, A. V.; Посыпанова, Г. А.; Попова, О Н; Moskaleva, E. Yu.; Северин, С. Е.

doi:10.1134/s0006297908070080

Cited by 7 publications

(6 citation statements)

References 16 publications

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“…As COV434-AMHRII cells, used as positive control, most of the cells expressing AMHRII showed diffuse, predominantly cytoplasmic immunostaining, with a moderate to strong intensity and constant membranous staining. This was in accordance with previous observations suggesting a high pool of intracellular AMHRII receptors in cancer cells [43] and regulation of AMHRII expression by intracellular retention [32]. Due to this distribution, a GHs was established, considering both cytoplasmic (Cy) and membranous (Mb) AMHRII expression: GHs = (Mb Intensity × Mb Frequency) + (Cy Intensity × Cy Frequency).…”

Section: Immunohistochemistrysupporting

confidence: 91%

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

Barret¹,

André

Jarry

et al. 2021

Biology

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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.

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Section: Immunohistochemistrysupporting

confidence: 91%

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

Barret¹,

André

Jarry

et al. 2021

Biology

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“…To consider other therapeutic agents that can target SP cells and NSP cells, we turned to extracellularly active receptor mediated agents and tested the effects of MIS, as mouse ovarian surface epithelium expresses MIS RII receptors (21,29,30), as do human ovarian cancer cell lines and primary ovarian cancer ascites cells (20). We found that MIS and its small molecule MISRII receptordependent agonist, SP600125 (23), significantly decreased SP cell percentages in OVCAR-5, IGROV-1, and SKOV-3.…”

Section: Discussionmentioning

confidence: 99%

Müllerian inhibiting substance preferentially inhibits stem/progenitors in human ovarian cancer cell lines compared with chemotherapeutics

Wei

Dombkowski

Meirelles

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Cancer stem cells are proposed to be tumor-initiating cells capable of tumorigenesis, recurrence, metastasis, and drug resistance, and, like somatic stem cells, are thought to be capable of unlimited selfrenewal and, when stimulated, proliferation and differentiation. Here we select cells by expression of a panel of markers to enrich for a population with stem cell-like characteristics. A panel of eight was initially selected from 95 human cell surface antigens as each was shared among human ovarian primary cancers, ovarian cancer cell lines, and normal fimbria. A total of 150 combinations of markers were reduced to a panel of three-CD44, CD24, and Epcam-which selected, in three ovarian cancer cell lines, those cells which best formed colonies. Cells expressing CD44, CD24, and Epcam exhibited stem cell characteristics of shorter tumor-free intervals in vivo after limiting dilution, and enhanced migration in invasion assays in vitro. Also, doxorubicin, cisplatin, and paclitaxel increased this enriched population which, conversely, was significantly inhibited by Mülle-rian inhibiting substance (MIS) or the MIS mimetic SP600125. These findings demonstrate that flow cytometry can be used to detect a population which shows differential drug sensitivity, and imply that treatment of patients can be individualized to target both stem/progenitor cell enriched and nonenriched subpopulations. The findings also suggest that this population, amenable to isolation by flow cytometry, can be used to screen for novel treatment paradigms, including biologic agents such as MIS, which will improve outcomes for patients with ovarian cancer.anthrapyrazolone | chemotherapy resistance | stem/progenitor cell-enriched populations A s evidence is accumulating to indicate that cancer could be a stem cell disease (1-4), it is becoming increasingly important to be able to identify cancer stem/progenitor cells and to develop treatment modalities that specifically target the stem cell enriched population, coupled with treatments effective against the larger population not enriched for stem cells. The concept of cancer stem cells has opened new areas of research in carcinogenesis, but has the more immediate translational potential of uncovering new treatment targets.We previously identified somatic label-retaining cells with stem cell features in ovarian surface epithelium (5), and with others (6, 7), postulate that somatic stem cells or their immediate progenitors can revert to cancer stem cells (8). It is also possible that the stem cells may remain the same, but that signals which control the stem/progenitor cell activity may change. Several recent studies have demonstrated that cancer stem cells may confer chemotherapeutic resistant ovarian tumor growth and metastasis (2, 9).Ovarian cancer is diagnosed in approximately 25,000 new cases per year in the United States and is associated with a 50% mortality rate (10, 11); more than 90% of cases are epithelial in origin (12, 13). Epithelial ovarian cancers fall into four main subtypes: mucinous,...

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“…AMHR2 is expressed in the prostate gland, prostate cancer cell lines, and human prostate adenocarcinomas [9]. AMH has been shown to inhibit the growth of human prostate cancer cell lines [89]. Additionally, because AMH suppresses testicular testosterone production and regulates androgen-induced gene expression and growth in prostate cancer cells, it may act via several synergistic mechanisms in the treatment of prostate cancer [90].…”

Section: Prostate Cancermentioning

confidence: 99%

Potential therapeutic applications of human anti-Müllerian hormone (AMH) analogues in reproductive medicine

Kushnir

Seifer

Barad

et al. 2017

J Assist Reprod Genet

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Members of the transforming growth factor-beta (TGF-beta) superfamily are key regulators of various physiological processes. Anti-Müllerian hormone (AMH) which is also commonly known as Müllerian-inhibiting substance (MIS) is a member of the TGF-beta superfamily and an important regulator of reproductive organ differentiation and ovarian follicular development. While AMH has been used for diagnostic purposes as a biomarker for over 15 years, new potential therapeutic applications of recombinant human AMH analogues are now emerging as pharmacologic agents in reproductive medicine. Therapeutic uses of AMH in gonadal tissue may provide a unique opportunity to address a broad range of reproductive themes, like contraception, ovulation induction, onset of menopause, and fertility preservation, as well as specific disease conditions, such as polycystic ovarian syndrome (PCOS) and cancers of the reproductive tract. This review explores the most promising therapeutic applications for a novel class of drugs known as AMH analogues with agonist and antagonist functions.

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Localization of Mullerian inhibiting substance receptors in various human cancer cell lines

Cited by 7 publications

References 16 publications

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

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

Müllerian inhibiting substance preferentially inhibits stem/progenitors in human ovarian cancer cell lines compared with chemotherapeutics

Potential therapeutic applications of human anti-Müllerian hormone (AMH) analogues in reproductive medicine

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