A Cellular Study of Inflammatory Responses in Women with Polycystic Ovary Syndrome as: “An In vitro Model of Anti-Breast Tumor Response”
- Articles
- Submited: March 25, 2021
-
Published: June 17, 2022
Abstract
Background: Although Polycystic Ovary syndrome is a common endocrine disorder among women of reproductive age; is unclear whether PCOS increases the risk of subsequent development of, Gynecologic cancers namely breast cancer. The present study is aimed to compare the anti-tumoral ability of peripheral blood mononuclear cells of women with PCOS with that of healthy controls using the co-culture system between effector cells and target tumor cell lines.
Methods: PBMCs were isolated from 25 women with PCOS and 25 healthy controls. Breast tumor cell lines were incubated as the two target cells and were cultured adjacent to PBMCs in the transwell co-culture system. Proliferation rate of the effectors cells evaluated by BrdU cell proliferation assay after 48 and 72 hours and T CD3+CD8+ lymphocytes were assessed using flow cytometry. Tumor necrosis factor alpha production was evaluated in cell culture supernatant by sandwich ELISA technique.
Results: After 48 hours incubation with tumor cell lines, the mean proliferation score of PBMCs was significantly higher in PCOS group compared to that of healthy controls (921.04 vs 287.6; P=0.002). In PCOS women, after 72 hours of incubation, TNF-α concentration was significantly reduced compared to 48-hour cultures (921.04±271.4 pg/dl vs 545.6±151.1 pg/dl at 48 h and 72 h intervals, P<0.05); it was increased in healthy controls.
Conclusion: The ability of PBMCs to produce TNF-α decreased gradually in PCOS group; as a result of which they may lack the ability required to form an in vitro efficient antitumor response to breast tumor cell lines.
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References
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[24] Wang R, Mol B.W. The Rotterdam criteria for polycystic ovary syndrome: evidence-based criteria? Hum Rep. 2017;32(2):261–264. https://doi.org/10.1093/humrep/dew287
[25] Hashemi S, Ramezani Tehrani F, Noroozzadeh M, Azizi F. Normal cut-off values for hyperandrogenaemia in Iranian women of reproductive age. Eur J Obstet Gynecol Reprod Biol. 2014;172: 51-55. https://doi.org/10.1016/j.ejogrb.2013.09.029
[26] North American Menopause Society. Menopause Practice: A Clinician's Guide. 3rd ed. 2007; Cleveland, OH: North American Menopause Society.
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[29] Havell EA, Fiers W, North RJ. The antitumor function of tumor necrosis factor (TNF) Therapeutic action of TNF against an established murine sarcoma is indirect, immunologically dependent, and limited by severe toxicity. J Exp Med. 1988;167(3):1067–1085. https://doi.org/10.1084/jem.167.3.1067
[30] Balkwill F. TNF-
[2] Tehrani FR, Simbar M, Tohidi M, Hosseinpanah F, Azizi F. The prevalence of polycystic ovary syndrome in a community sample of Iranian population: Iranian PCOS prevalence study. Rep Biol Endocrinol. 2011; 9(1): 39.
[3] Pasquali R, Stener‐Victorin E, Yildiz BO, Duleba AJ, Hoeger K, Mason H, et al. PCOS Forum: research in polycystic ovary syndrome today and tomorrow. Clin endocrinol. 2011; 74(4): 424-433. doi.org/10.1111/j.1365-2265.2010.03956.x
[4] Azziz R, Sanchez L, Knochenhauer E, Moran C, Lazenby J, Stephens K, et al. Androgen excess in women: Experience with over 1000 consecutive patients. J Clin Endocrinol Metabol. 2004; 89(2): 453-462. https://doi.org/10.1210/jc.2003-031122
[5] Fanta M, Cibula D, Vrbíková J. Prevalence of Nonclassic Adrenal Hyperplasia (NCAH) in hyperandrogenic women. Gynecol Endocrinol. 2008;24(3):154-157. https://doi.org/10.1080/09513590801911992
[6] González F, Rote NS, Minium J, Kirwan JP. Increased activation of nuclear factor κB triggers inflammation and insulin resistance in polycystic ovary syndrome. J Clin Endocrinol Metabol. 2006; 91(4): 1508-1512. https://doi.org/10.1210/jc.2005-2327
[7] Schüring A, Schulte N, Sonntag B, Kiesel L. Androgens and insulin–two key players in polycystic ovary syndrome. Gynäkol geburtshilfliche Rundschau. 2008;48(1):9-15. DOI: 10.1159/000111465
[8] Duleba AJ, Dokras A. Is PCOS an inflammatory process? Fertil steril. 2012;97(1):7-12.
https://doi.org/10.1016/j.fertnstert.2011.11.023
[9] Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. cancer J clin. 2011;61(2):69-90. doi.org/10.3322/caac.20107
[10] Sadjadi A, Nouraie M, Mohagheghi MA, Mousavi-Jarrahi A, Malekezadeh R, Parkin DM. Cancer occurrence in Iran in 2002, an international perspective. Asian Pac J cancer prev. 2005;6(3):359.
[11] Mollie B, Boeke C, Tamimi R (2005) Established breast cancer risk factors and risk of intrinsic tumor subtypes. BBA Rev Cancer. 2005;1856(1):73-85. https://doi.org/10.1016/j.bbcan.2015.06.002
[12] Srabović N, Mujagić Z, Mujanović-Mustedanagić J, Muminović Z, Čičkušić E. Interleukin 18 expression in the primary breast cancer tumour tissue. Official Publication of the Medical Association of Zenica-Doboj Canton Bosnia and Herzegovina. 2011;8(1):109.
[13] Zhang Y-f, Yang Y-s, Hong J, Gu W-q, Shen C-f, Xu M, et al. (2006) Elevated serum levels of interleukin-18 are associated with insulin resistance in women with polycystic ovary syndrome. Endocrine 29(3): 419-423.
[14] Dethlefsen C, Hojfeldt G, Hojman P. The role of intratumoral and systemic IL-6 in breast cancer. Breast cancer res treat. 2013;138(3):657-664.
[15] Hove T, Corbaz A, Amitai H, Aloni S, Belzer I, Graber P, et al. Blockade of endogenous IL-18 ameliorates TNBS-induced colitis by decreasing local TNF-α production in mice. Gastroenterol. 2001;121(6):1372-1379. https://doi.org/10.1053/gast.2001.29579
[16] Escobar-Morreale HF, Botella-Carretero JI, Villuendas G, Sancho J, San Millán JL. Serum interleukin-18 concentrations are increased in the polycystic ovary syndrome: relationship to insulin resistance and to obesity. J Clin Endocrinol Metabol. 2004;89(2):806-811. https://doi.org/10.1210/jc.2003-031365
[17] de Jager SC, Kraaijeveld AO, Grauss RW, de Jager W, Liem SS, van der Hoeven BL, et al. CCL3 (MIP-1a) levels are elevated during acute coronary syndromes and show strong prognostic power for future ischemic events. J Mol Cell Cardiol. 2008;45(3): 446-452. https://doi.org/10.1016/j.yjmcc.2008.06.003
[18] Zangeneh FZ, Naghizadeh MM, Masoumi M. Polycystic ovary syndrome and circulating inflammatory markers. Inter J Rep Biomedicine. 2017;15(6):375-382. PMID: 29177240
[19] Diamanti‐Kandarakis E, Alexandraki K, Piperi C, Protogerou A, Katsikis I, Paterakis T, et al. Inflammatory and endothelial markers in women with polycystic ovary syndrome. Eur J clin invest. 2006;36(10):691-697. https://doi.org/10.1111/j.1365-2362.2006.01712.x
[20] Meikle AW, Dorchuck RW, Araneo BA, Stringham JD, Evans TG, Spruance SL, et al. The presence of a dehydroepiandrosterone-specific receptor binding complex in murine T cells. J steroid biochem mol biol. 1992;42(3):293-304. https://doi.org/10.1016/0960-0760(92)90132-3
[21] Dimitrakakis C, Bondy C. Androgens and the breast. Breast Cancer Res. 2009;11(5):212.
[22] Secreto G, Venturelli E, Pasanisi P, Berrino F. Androgens and breast cancer. The hyperandrogenic theory of breast cancer: past, present and future. Frontiers in Breast Cancer Res. 2007;39.
[23] Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertility sterility. 2004;81(1):19-25. https://doi.org/10.1016/j.fertnstert.2003.10.004
[24] Wang R, Mol B.W. The Rotterdam criteria for polycystic ovary syndrome: evidence-based criteria? Hum Rep. 2017;32(2):261–264. https://doi.org/10.1093/humrep/dew287
[25] Hashemi S, Ramezani Tehrani F, Noroozzadeh M, Azizi F. Normal cut-off values for hyperandrogenaemia in Iranian women of reproductive age. Eur J Obstet Gynecol Reprod Biol. 2014;172: 51-55. https://doi.org/10.1016/j.ejogrb.2013.09.029
[26] North American Menopause Society. Menopause Practice: A Clinician's Guide. 3rd ed. 2007; Cleveland, OH: North American Menopause Society.
[27] Virchow R. Die Krankhaften Geschw¨ulste, Berlin, Germany. 1863.
[28] Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? The Lancet. 2001;357(9255):539–545. https://doi.org/10.1016/S0140-6736(00)04046-0
[29] Havell EA, Fiers W, North RJ. The antitumor function of tumor necrosis factor (TNF) Therapeutic action of TNF against an established murine sarcoma is indirect, immunologically dependent, and limited by severe toxicity. J Exp Med. 1988;167(3):1067–1085. https://doi.org/10.1084/jem.167.3.1067
[30] Balkwill F. TNF-
How to Cite
1.
A Cellular Study of Inflammatory Responses in Women with Polycystic Ovary Syndrome as: “An In vitro Model of Anti-Breast Tumor Response”. Journal of Research and Opinion [Internet]. 2022 Jun. 17 [cited 2024 Nov. 24];9(5). Available from: https://researchopinion.in/index.php/jro/article/view/97
