期刊论文详细信息
Journal of Experimental & Clinical Cancer Research
Anti-mullerian hormone is expressed by endometriosis tissues and induces cell cycle arrest and apoptosis in endometriosis cells
Alfonso Baldi1  Francesca Petraglia1  Pietro G Signorile1 
[1] Centro Italiano Endometriosi, Via Aurelia, 559, Rome 00165, Italy
关键词: Apoptosis;    AMH;    Immunohistochemistry;    Endometriosis;   
Others  :  801175
DOI  :  10.1186/1756-9966-33-46
 received in 2014-04-18, accepted in 2014-05-19,  发布年份 2014
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【 摘 要 】

Background

The anti-mullerian hormone (AMH) is a member of the transforming growth factor β (TGF-β) superfamily, which is responsible of the regression of the mullerian duct. AMH is expressed in the normal endometrium, where, acting in a paracrine fashion, negatively regulates cellular viability. Our objective was to evaluate the in vitro effects of the treatment with AMH of endometriosic cells.

Methods

AMH expression in human endometriosis glands was evaluated by immunohistochemistry. RT-PCR has been used to quantify the expression levels of AMH and AMH RII isoforms, as well as of cytochrome P450 in both endometriosis epithelial and stromal cells Effects of AMH and AMH-cleaved treatment in endometriosis cells were evaluated by flow-cytometry analysis. Finally, it has been evaluated the effect of plasmin-digested AMH on cytochrome P450 activity.

Results

AMH and AMH RII isoforms, as well as cytochrome P450, were expressed in both endometriosis epithelial and stromal cells. Treatment of endometriosis stromal and epithelial cell growth with AMH was able to induce a decrease in the percentage of cells in S phase and increase percentage of cells in G1 and G2 phase; coherently, decreased cell viability and increased percentage of cells death fraction was observed. The plasmin-digested AMH was able to suppress most of the cytochrome P450 activity, causing an increase of pre-G1 phase and of apoptosis induction treating with plasmin-digested AMH in both cell lines, most marked in the epithelial cells.

Conclusions

The data produced suggest a possible use of AMH as therapeutic agents in endometriosis.

【 授权许可】

   
2014 Signorile et al.; licensee BioMed Central Ltd.

【 预 览 】
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【 参考文献 】
  • [1]Bulun SE: Endometriosis. New Engl J Med 2009, 360:268-279.
  • [2]Cramer DW, Missmer SA: The epidemiology of endometriosis. Ann N Y Acad Sci 2002, 955:11-22.
  • [3]Baldi A, Campioni M, Signorile PG: Endometriosis: pathogenesis, diagnosis, therapy and association with cancer. Oncol Rep 2008, 19:843-846.
  • [4]Signorile PG, Spugnini EP, Citro G, Viceconte R, Vincenzi B, Baldi F, Baldi A: Endocrine disruptors in utero cause ovarian damages linked to endometriosis. Front Biosci 2012, 4:1724-1730.
  • [5]Signorile PG, Baldi F, Bussani R, D’Armiento M, De Falco M, Baldi A: Ectopic endometrium in human foetuses is a common event and sustains the theory of mullerianosis in the pathogenesis of endometriosis, a disease that predisposes to cancer. J Exp Clin Cancer Res 2009, 28:49. BioMed Central Full Text
  • [6]Signorile PG, Baldi F, Bussani R, D’Armiento M, De Falco M, Boccellino M, Quagliuolo L, Baldi A: New evidences sustaining the presence of endometriosis in the human foetus. RBM online 2010, 21:142-147.
  • [7]Signorile PG, Baldi F, Bussani R, Viceconte R, Bulzomi P, D’Armiento M, D’Avino A, Baldi A: Embryologic origin of endometriosis: analysis of 101 human female foetuses. J Cell Physiol 2012, 227:1653-1656.
  • [8]Signorile PG, Baldi A: Endometriosis: new concepts in the pathogenesis. Int J Biochem Cell Biol 2010, 42:778-780.
  • [9]Crispi S, Piccolo MT, D’Avino A, Donizetti A, Viceconte R, Spyrou M, Calogero RA, Baldi A, Signorile PG: Transcriptional profiling of endometriosis tissues identifies genes related to organogenesis defects. J Cell Physiol 2013, 228:1927-1934.
  • [10]La Marca A, Broekmans FJ, Volpe A, Fauser BC, Macklon NS, ESHRE Special Interest Group for Reproductive Endocrinology–AMH Round Table: Anti-Mullerian hormone (AMH): what do we still need to know? Hum Reproduct 2009, 24:2264-2275.
  • [11]Tal R, Seifer DB: Potential mechanisms for racial and ethnic differences in antimüllerian hormone and ovarian reserve. Int J Endocrinol 2013, 2013:818912.
  • [12]Wang J, Dicken C, Lustbader JW, Tortoriello DV: Evidence for a Mullerian-inhibiting substance autocrine/paracrine system in adult human endometrium. Fertil Steril 2009, 91:1195-1203.
  • [13]Boccellino M, Quagliuolo L, Verde A, La Porta R, Crispi S, Piccolo MT, Vitiello A, Baldi A, Signorile PG: In vitro model of stromal and epithelial immortalized endometriotic cells. J Cell Biochem 2012, 113:1292-1301.
  • [14]Pepinsky RB, Sinclair LK, Chow EP, Mattaliano RJ, Manganaro TF, Donahoe PK, Cate RL: Proteolytic processing of mullerian inhibiting substance produces a transforming growth factor-beta-like fragment. J Biol Chem 1988, 263:18961-18964.
  • [15]Grossman MP, Nakajima ST, Fallat ME, Siow Y: Mullerian-inhibiting substance inhibits cytochrome P450 aromatase activity in human granulosa lutein cell culture. Fertil Steril 2008, 89:1364-1370.
  • [16]Nebbioso A, Clarke N, Voltz E, Germain E, Ambrosino C, Bontempo P, Alvarez R, Schiavone EM, Ferrara F, Bresciani F, Weisz A, de Lera AR, Gronemeyer H, Altucci L: Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells. Nat Med 2005, 11:77-84.
  • [17]Giudice LC, Kao LC: Endometriosis. Lancet 2004, 364:1789-1799.
  • [18]Bruner-Tran KL, Osteen KG, Taylor HS, Sokalska A, Haines K, Duleba AJ: Resveratrol inhibits development of experimental endometriosis in vivo and reduces endometrial stromal cell invasiveness in vitro. Biol Reprod 2011, 84:106-112.
  • [19]Pitsos M, Kanakas N: The role of matrix metalloproteinases in the pathogenesis of endometriosis. Reprod Sci 2009, 16:717-726.
  • [20]Nezhat FR, Pejovic T, Reis FM, Guo SW: The link between endometriosis and ovarian cancer: clinical implications. Int J Gynecol Cancer 2014, 24:623-628.
  • [21]Melin A, Sparen P, Bergqvist A: Endometriosis and the risk of cancer with special emphasis on ovarian cancer. Hum Reprod 2006, 21:1237-1242.
  • [22]Hornstein MD, Thomas PP, Sober AJ, Wyshak G, Albright NL, Frisch RE: Association between endometriosis, dysplastic nevi and history of melanoma in women of reproductive age. Human Reprod 1997, 1997(12):143-145.
  • [23]Bertelsen L, Mellemkjer L, Frederiksen K, Kyer SK, Brinton LA, Sakoda LC, van Valkengoed I, Olsen JH: Risk for breast cancer among women with endometriosis. Int J Cancer 2007, 120:1372-1375.
  • [24]Varma R, Rollason T, Gupta JK, Maher ER: Endometriosis and the neoplastic process. Reproduction 2004, 127:293-304.
  • [25]Durlinger ALL, Gruijters MJG, Kramer P, Karels B, Ingraham HA, Nachtigal MW, Uilenbroek JT, Grootegoed JA, Themmen AP: Anti-Mullerian hormone inhibits initiation of primordial follicle growth in the mouse ovary. Endocrinology 2002, 143:3836-3844.
  • [26]Visser JA, Schipper I, Laven JS, Themmen AP: Anti-Müllerian hormone: an ovarian reserve marker in primary ovarian insufficiency. Nat Rev Endocrinol 2012, 8:331-341.
  • [27]Renaud EJ, MacLaughlin DT, Oliva E, Rueda BR, Donahoe PK: Endometrial cancer is a receptor-mediated target for Mullerian inihibiting substance. Proc Natl Acad Sci U S A 2005, 102:111-116.
  • [28]Stephen AE, Pearsall LA, Christian BP, Donahoe PK, Vacanti JP, MacLaughlin DT: Highly purified müllerian inhibiting substance inhibits human ovarian cancer in vivo. Clin Cancer Res 2002, 8:2640-2646.
  • [29]Wei X, Dombkowski D, Meirelles K, Pieretti-Vanmarcke R, Szotek PP, Chang HL, Preffer FI, Mueller PR, Teixeira J, MacLaughlin DT, Donahoe PK: Mullerian inhibiting substance preferentially inhibits stem/progenitors in human ovarian cancer cell lines compared with chemotherapeutics. Proc Natl Acad Sci U S A 2010, 107:18874-18879.
  • [30]Chang HL, Pieretti-Vanmarcke R, Nicolaou F, Li X, Wei X, MacLaughlin DT, Donahoe PK: Mullerian inhibiting substance inhibits invasion and migration of epithelial cancer cell lines. Gynecol Oncol 2011, 120:128-134.
  • [31]Bakkum-Gamez JN, Aletti G, Lewis KA, Keeney GL, Thomas BM, Navarro-Teulon I, Cliby WA: Mullerian inhibiting substance tyoe II receptor (MISIIR): a novel tissue-specific target expressed by gynecologic cancers. Gynecol Oncol 2008, 108:141-148.
  • [32]Namkung J, Song JY, Jo HH, Kim MR, Lew YO, Donahoe PK, MacLaughlin DT, Kim JH: Mullerian inhibiting substance induces apoptosis of human endometrial stromal cells in endometriosis. J Clin Endocrinol Metab 2012, 97:3224-3230.
  • [33]Borahay MA, Lu F, Ozpolat B, Tekedereli I, Gurates B, Karipcin S, Kilic GS: Mullerian inhibiting substance suppresses proliferation and induces apoptosis and autophagy in endometriosis cells in vitro. ISRN Obstet Gynecol 2013, 2013:361489.
  • [34]Pépin D, Hoang M, Nicolaou F, Hendren K, Benedict LA, Al-Moujahed A, Sosulski A, Marmalidou A, Vavvas D, Donahoe PK: An albumin leader sequence coupled with a cleavage site modification enhances the yield of recombinant C-terminal Mullerian Inhibiting Substance. Technology 2013, 1:63-71.
  • [35]Rey R, Lukas-Croisier C, Lasala C, Bedecarrás P: AMH/MIS: what we know already about the gene, the protein and its regulation. Mol Cell Endocrinol 2003, 211:21-31.
  • [36]di Clemente N, Jamin SP, Lugovskoy A, Carmillo P, Ehrenfels C, Picard JY, Whitty A, Josso N, Pepinsky RB, Cate RL: Processing of anti-mullerian hormone regulates receptor activation by a mechanism distinct from TGF-β. Mol Endocrinol 2010, 24:2193-2206.
  • [37]Attar E, Bulun SE: Aromatase and other steroidogenic genes in endometriosis: translational aspects. Hum Reprod Update 2006, 12:49-56.
  • [38]Simpson ER, Clyne C, Rubin G, Boon WC, Robertson K, Britt K, Speed C, Jones M: Aromatase—a brief overview. Annu Rev Physiol 2002, 64:93-127.
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