Prostate stromal cells express the progesterone receptor to control cancer cell mobility.

<h4>Background</h4>Reciprocal interactions between epithelium and stroma play vital roles for prostate cancer development and progression. Enhanced secretions of cytokines and growth factors by cancer associated fibroblasts in prostate tumors create a favorable microenvironment for cance...

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Autores principales: Yue Yu, Jennifer Suehyun Lee, Ning Xie, Estelle Li, Antonio Hurtado-Coll, Ladan Fazli, Michael Cox, Stephen Plymate, Martin Gleave, Xuesen Dong
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Publicado: Public Library of Science (PLoS) 2014
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spelling oai:doaj.org-article:12681f314f5445559eabc019ebbb64002021-11-18T08:26:25ZProstate stromal cells express the progesterone receptor to control cancer cell mobility.1932-620310.1371/journal.pone.0092714https://doaj.org/article/12681f314f5445559eabc019ebbb64002014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24664419/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Reciprocal interactions between epithelium and stroma play vital roles for prostate cancer development and progression. Enhanced secretions of cytokines and growth factors by cancer associated fibroblasts in prostate tumors create a favorable microenvironment for cancer cells to grow and metastasize. Our previous work showed that the progesterone receptor (PR) was expressed specifically in prostate stromal fibroblasts and smooth muscle cells. However, the expression levels of PR and its impact to tumor microenvironment in prostate tumors are poorly understood.<h4>Methods</h4>Immunohistochemistry assays are applied to human prostate tissue biopsies. Cell migration, invasion and proliferation assays are performed using human prostate cells. Real-time PCR and ELISA are applied to measure gene expression at molecular levels.<h4>Results</h4>Immunohistochemistry assays showed that PR protein levels were decreased in cancer associated stroma when compared with paired normal prostate stroma. Using in vitro prostate stromal cell models, we showed that conditioned media collected from PR positive stromal cells inhibited prostate cancer cell migration and invasion, but had minor suppressive impacts on cancer cell proliferation. PR suppressed the secretion of stromal derived factor-1 (SDF-1) and interlukin-6 (IL-6) by stromal cells independent to PR ligands. Blocking PR expression by siRNA or supplementation of exogenous SDF-1 or IL-6 to conditioned media from PR positive stromal cells counteracted the inhibitory effects of PR to cancer cell migration and invasion.<h4>Conclusions</h4>Decreased expression of the PR in cancer associated stroma may contribute to the elevated SDF-1 and IL-6 levels in prostate tumors and enhance prostate tumor progression.Yue YuJennifer Suehyun LeeNing XieEstelle LiAntonio Hurtado-CollLadan FazliMichael CoxStephen PlymateMartin GleaveXuesen DongPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e92714 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yue Yu
Jennifer Suehyun Lee
Ning Xie
Estelle Li
Antonio Hurtado-Coll
Ladan Fazli
Michael Cox
Stephen Plymate
Martin Gleave
Xuesen Dong
Prostate stromal cells express the progesterone receptor to control cancer cell mobility.
description <h4>Background</h4>Reciprocal interactions between epithelium and stroma play vital roles for prostate cancer development and progression. Enhanced secretions of cytokines and growth factors by cancer associated fibroblasts in prostate tumors create a favorable microenvironment for cancer cells to grow and metastasize. Our previous work showed that the progesterone receptor (PR) was expressed specifically in prostate stromal fibroblasts and smooth muscle cells. However, the expression levels of PR and its impact to tumor microenvironment in prostate tumors are poorly understood.<h4>Methods</h4>Immunohistochemistry assays are applied to human prostate tissue biopsies. Cell migration, invasion and proliferation assays are performed using human prostate cells. Real-time PCR and ELISA are applied to measure gene expression at molecular levels.<h4>Results</h4>Immunohistochemistry assays showed that PR protein levels were decreased in cancer associated stroma when compared with paired normal prostate stroma. Using in vitro prostate stromal cell models, we showed that conditioned media collected from PR positive stromal cells inhibited prostate cancer cell migration and invasion, but had minor suppressive impacts on cancer cell proliferation. PR suppressed the secretion of stromal derived factor-1 (SDF-1) and interlukin-6 (IL-6) by stromal cells independent to PR ligands. Blocking PR expression by siRNA or supplementation of exogenous SDF-1 or IL-6 to conditioned media from PR positive stromal cells counteracted the inhibitory effects of PR to cancer cell migration and invasion.<h4>Conclusions</h4>Decreased expression of the PR in cancer associated stroma may contribute to the elevated SDF-1 and IL-6 levels in prostate tumors and enhance prostate tumor progression.
format article
author Yue Yu
Jennifer Suehyun Lee
Ning Xie
Estelle Li
Antonio Hurtado-Coll
Ladan Fazli
Michael Cox
Stephen Plymate
Martin Gleave
Xuesen Dong
author_facet Yue Yu
Jennifer Suehyun Lee
Ning Xie
Estelle Li
Antonio Hurtado-Coll
Ladan Fazli
Michael Cox
Stephen Plymate
Martin Gleave
Xuesen Dong
author_sort Yue Yu
title Prostate stromal cells express the progesterone receptor to control cancer cell mobility.
title_short Prostate stromal cells express the progesterone receptor to control cancer cell mobility.
title_full Prostate stromal cells express the progesterone receptor to control cancer cell mobility.
title_fullStr Prostate stromal cells express the progesterone receptor to control cancer cell mobility.
title_full_unstemmed Prostate stromal cells express the progesterone receptor to control cancer cell mobility.
title_sort prostate stromal cells express the progesterone receptor to control cancer cell mobility.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/12681f314f5445559eabc019ebbb6400
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