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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Frontiers Media S.A.
2021
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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) |
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peritoneal fluid FoxP3 EZH2 endometriosis ovarian cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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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 |
work_keys_str_mv |
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_version_ |
1718406004485390336 |