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Fallopian Tube-Derived Tumor Cells Induce Testosterone Secretion from the Ovary, Increasing Epithelial Proliferation and Invasion

SIMPLE SUMMARY: The area between the fallopian tube and the ovary is of interest since the ends of the fimbria are the progenitor site for high grade serous cancer. Metabolomics revealed that androgens are induced at this site, which then increased proliferation of normal fallopian tube cells and th...

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Autores principales: Colina, Jose A., Zink, Katherine E., Eliadis, Kanella, Salehi, Reza, Gargus, Emma S., Wagner, Sarah R., Moss, Kristine J., Baligod, Seth, Li, Kailiang, Kirkpatrick, Brenna J., Woodruff, Teresa K., Tsang, Benjamin K., Sanchez, Laura M., Burdette, Joanna E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073317/
https://www.ncbi.nlm.nih.gov/pubmed/33923536
http://dx.doi.org/10.3390/cancers13081925
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author Colina, Jose A.
Zink, Katherine E.
Eliadis, Kanella
Salehi, Reza
Gargus, Emma S.
Wagner, Sarah R.
Moss, Kristine J.
Baligod, Seth
Li, Kailiang
Kirkpatrick, Brenna J.
Woodruff, Teresa K.
Tsang, Benjamin K.
Sanchez, Laura M.
Burdette, Joanna E.
author_facet Colina, Jose A.
Zink, Katherine E.
Eliadis, Kanella
Salehi, Reza
Gargus, Emma S.
Wagner, Sarah R.
Moss, Kristine J.
Baligod, Seth
Li, Kailiang
Kirkpatrick, Brenna J.
Woodruff, Teresa K.
Tsang, Benjamin K.
Sanchez, Laura M.
Burdette, Joanna E.
author_sort Colina, Jose A.
collection PubMed
description SIMPLE SUMMARY: The area between the fallopian tube and the ovary is of interest since the ends of the fimbria are the progenitor site for high grade serous cancer. Metabolomics revealed that androgens are induced at this site, which then increased proliferation of normal fallopian tube cells and their migration. ABSTRACT: The fallopian tube epithelium is the site of origin for a majority of high grade serous ovarian carcinomas (HGSOC). The chemical communication between the fallopian tube and the ovary in the development of HGSOC from the fallopian tube is of interest since the fimbriated ends in proximity of the ovary harbor serous tubal intraepithelial carcinoma (STICs). Epidemiological data indicates that androgens play a role in ovarian carcinogenesis; however, the oncogenic impact of androgen exposure on the fallopian tube, or tubal neoplastic precursor lesions, has yet to be explored. In this report, imaging mass spectrometry identified that testosterone is produced by the ovary when exposed to tumorigenic fallopian tube derived PTEN deficient cells. Androgen exposure increased cellular viability, proliferation, and invasion of murine cell models of healthy fallopian tube epithelium and PAX2 deficient models of the preneoplastic secretory cell outgrowths (SCOUTs). Proliferation and invasion induced by androgen was reversed by co-treatment with androgen receptor (AR) antagonist, bicalutamide. Furthermore, ablation of phosphorylated ERK reversed proliferation, but not invasion. Investigation of two hyperandrogenic rodent models of polycystic ovarian syndrome revealed that peripheral administration of androgens does not induce fallopian proliferation in vivo. These data suggest that tumorigenic lesions in the fallopian tube may induce an androgenic microenvironment proximal to the ovary, which may in turn promote proliferation of the fallopian tube epithelium and preneoplastic lesions.
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spelling pubmed-80733172021-04-27 Fallopian Tube-Derived Tumor Cells Induce Testosterone Secretion from the Ovary, Increasing Epithelial Proliferation and Invasion Colina, Jose A. Zink, Katherine E. Eliadis, Kanella Salehi, Reza Gargus, Emma S. Wagner, Sarah R. Moss, Kristine J. Baligod, Seth Li, Kailiang Kirkpatrick, Brenna J. Woodruff, Teresa K. Tsang, Benjamin K. Sanchez, Laura M. Burdette, Joanna E. Cancers (Basel) Article SIMPLE SUMMARY: The area between the fallopian tube and the ovary is of interest since the ends of the fimbria are the progenitor site for high grade serous cancer. Metabolomics revealed that androgens are induced at this site, which then increased proliferation of normal fallopian tube cells and their migration. ABSTRACT: The fallopian tube epithelium is the site of origin for a majority of high grade serous ovarian carcinomas (HGSOC). The chemical communication between the fallopian tube and the ovary in the development of HGSOC from the fallopian tube is of interest since the fimbriated ends in proximity of the ovary harbor serous tubal intraepithelial carcinoma (STICs). Epidemiological data indicates that androgens play a role in ovarian carcinogenesis; however, the oncogenic impact of androgen exposure on the fallopian tube, or tubal neoplastic precursor lesions, has yet to be explored. In this report, imaging mass spectrometry identified that testosterone is produced by the ovary when exposed to tumorigenic fallopian tube derived PTEN deficient cells. Androgen exposure increased cellular viability, proliferation, and invasion of murine cell models of healthy fallopian tube epithelium and PAX2 deficient models of the preneoplastic secretory cell outgrowths (SCOUTs). Proliferation and invasion induced by androgen was reversed by co-treatment with androgen receptor (AR) antagonist, bicalutamide. Furthermore, ablation of phosphorylated ERK reversed proliferation, but not invasion. Investigation of two hyperandrogenic rodent models of polycystic ovarian syndrome revealed that peripheral administration of androgens does not induce fallopian proliferation in vivo. These data suggest that tumorigenic lesions in the fallopian tube may induce an androgenic microenvironment proximal to the ovary, which may in turn promote proliferation of the fallopian tube epithelium and preneoplastic lesions. MDPI 2021-04-16 /pmc/articles/PMC8073317/ /pubmed/33923536 http://dx.doi.org/10.3390/cancers13081925 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Colina, Jose A.
Zink, Katherine E.
Eliadis, Kanella
Salehi, Reza
Gargus, Emma S.
Wagner, Sarah R.
Moss, Kristine J.
Baligod, Seth
Li, Kailiang
Kirkpatrick, Brenna J.
Woodruff, Teresa K.
Tsang, Benjamin K.
Sanchez, Laura M.
Burdette, Joanna E.
Fallopian Tube-Derived Tumor Cells Induce Testosterone Secretion from the Ovary, Increasing Epithelial Proliferation and Invasion
title Fallopian Tube-Derived Tumor Cells Induce Testosterone Secretion from the Ovary, Increasing Epithelial Proliferation and Invasion
title_full Fallopian Tube-Derived Tumor Cells Induce Testosterone Secretion from the Ovary, Increasing Epithelial Proliferation and Invasion
title_fullStr Fallopian Tube-Derived Tumor Cells Induce Testosterone Secretion from the Ovary, Increasing Epithelial Proliferation and Invasion
title_full_unstemmed Fallopian Tube-Derived Tumor Cells Induce Testosterone Secretion from the Ovary, Increasing Epithelial Proliferation and Invasion
title_short Fallopian Tube-Derived Tumor Cells Induce Testosterone Secretion from the Ovary, Increasing Epithelial Proliferation and Invasion
title_sort fallopian tube-derived tumor cells induce testosterone secretion from the ovary, increasing epithelial proliferation and invasion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073317/
https://www.ncbi.nlm.nih.gov/pubmed/33923536
http://dx.doi.org/10.3390/cancers13081925
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