Peritoneal Modulators of Endometriosis-Associated Ovarian Cancer

Ovarian cancer is the 4th largest cause of cancer death in women. Approximately 10–15% of women of childbearing age suffer from endometriosis. Endometriosis is defined by the growth and presence of endometrial tissue (lesions) outside of the uterus. The women with endometriosis also have an increase...

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Autores principales: Sarah Brunty, Lauren Clower, Brenda Mitchell, Taylor Fleshman, Nadim Bou Zgheib, Nalini Santanam
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:0e1e9013e1f845cb9dd7e534b0ab3b692021-12-01T01:08:45ZPeritoneal Modulators of Endometriosis-Associated Ovarian Cancer2234-943X10.3389/fonc.2021.793297https://doaj.org/article/0e1e9013e1f845cb9dd7e534b0ab3b692021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.793297/fullhttps://doaj.org/toc/2234-943XOvarian cancer is the 4th largest cause of cancer death in women. Approximately 10–15% of women of childbearing age suffer from endometriosis. Endometriosis is defined by the growth and presence of endometrial tissue (lesions) outside of the uterus. The women with endometriosis also have an increased presence of peritoneal fluid (PF) that comprises of inflammatory cells, growth factors, cytokines/chemokines, etc. Epidemiological studies have shown that >3% of women with endometriosis develop ovarian cancer (low-grade serous or endometrioid types). Our hypothesis is that the PF from women with endometriosis induces transformative changes in the ovarian cells, leading to ovarian cancer development. PF from women with and without endometriosis was collected after IRB approval and patient consent. IOSE (human normal ovarian epithelial cells) and TOV-21G cells (human ovarian clear cell carcinoma cell line) were treated with various volumes of PF (no endometriosis or endometriosis) for 48 or 96 h and proliferation measured. Expression levels of epigenetic regulators and FoxP3, an inflammatory tumor suppressor, were determined. A Human Cancer Inflammation and Immunity Crosstalk RT2 Profiler PCR array was used to measure changes in cancer related genes in treated cells. Results showed increased growth of TOV-21G cells treated with PF from women with endometriosis versus without endometriosis and compared to IOSE cells. Endo PF treatment induced EZH2, H3K27me3, and FoxP3. The RT2 PCR array of TOV-21G cells treated with endo PF showed upregulation of various inflammatory genes (TLRs, Myd88, etc.). These studies indicate that PF from women with endometriosis can both proliferate and transform ovarian cells and hence this microenvironment plays a major mechanistic role in the progression of endometriosis to ovarian cancer.Sarah BruntyLauren ClowerBrenda MitchellTaylor FleshmanNadim Bou ZgheibNalini SantanamFrontiers Media S.A.articleperitoneal fluidFoxP3EZH2endometriosisovarian cancerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution DOAJ
collection DOAJ
language EN
topic peritoneal fluid
FoxP3
EZH2
endometriosis
ovarian cancer
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle peritoneal fluid
FoxP3
EZH2
endometriosis
ovarian cancer
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Sarah Brunty
Lauren Clower
Brenda Mitchell
Taylor Fleshman
Nadim Bou Zgheib
Nalini Santanam
Peritoneal Modulators of Endometriosis-Associated Ovarian Cancer
description Ovarian cancer is the 4th largest cause of cancer death in women. Approximately 10–15% of women of childbearing age suffer from endometriosis. Endometriosis is defined by the growth and presence of endometrial tissue (lesions) outside of the uterus. The women with endometriosis also have an increased presence of peritoneal fluid (PF) that comprises of inflammatory cells, growth factors, cytokines/chemokines, etc. Epidemiological studies have shown that >3% of women with endometriosis develop ovarian cancer (low-grade serous or endometrioid types). Our hypothesis is that the PF from women with endometriosis induces transformative changes in the ovarian cells, leading to ovarian cancer development. PF from women with and without endometriosis was collected after IRB approval and patient consent. IOSE (human normal ovarian epithelial cells) and TOV-21G cells (human ovarian clear cell carcinoma cell line) were treated with various volumes of PF (no endometriosis or endometriosis) for 48 or 96 h and proliferation measured. Expression levels of epigenetic regulators and FoxP3, an inflammatory tumor suppressor, were determined. A Human Cancer Inflammation and Immunity Crosstalk RT2 Profiler PCR array was used to measure changes in cancer related genes in treated cells. Results showed increased growth of TOV-21G cells treated with PF from women with endometriosis versus without endometriosis and compared to IOSE cells. Endo PF treatment induced EZH2, H3K27me3, and FoxP3. The RT2 PCR array of TOV-21G cells treated with endo PF showed upregulation of various inflammatory genes (TLRs, Myd88, etc.). These studies indicate that PF from women with endometriosis can both proliferate and transform ovarian cells and hence this microenvironment plays a major mechanistic role in the progression of endometriosis to ovarian cancer.
format article
author Sarah Brunty
Lauren Clower
Brenda Mitchell
Taylor Fleshman
Nadim Bou Zgheib
Nalini Santanam
author_facet Sarah Brunty
Lauren Clower
Brenda Mitchell
Taylor Fleshman
Nadim Bou Zgheib
Nalini Santanam
author_sort Sarah Brunty
title Peritoneal Modulators of Endometriosis-Associated Ovarian Cancer
title_short Peritoneal Modulators of Endometriosis-Associated Ovarian Cancer
title_full Peritoneal Modulators of Endometriosis-Associated Ovarian Cancer
title_fullStr Peritoneal Modulators of Endometriosis-Associated Ovarian Cancer
title_full_unstemmed Peritoneal Modulators of Endometriosis-Associated Ovarian Cancer
title_sort peritoneal modulators of endometriosis-associated ovarian cancer
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/0e1e9013e1f845cb9dd7e534b0ab3b69
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AT laurenclower peritonealmodulatorsofendometriosisassociatedovariancancer
AT brendamitchell peritonealmodulatorsofendometriosisassociatedovariancancer
AT taylorfleshman peritonealmodulatorsofendometriosisassociatedovariancancer
AT nadimbouzgheib peritonealmodulatorsofendometriosisassociatedovariancancer
AT nalinisantanam peritonealmodulatorsofendometriosisassociatedovariancancer
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