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Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate
Androgens are essential for the development, differentiation, growth, and function of the prostate through epithelial–stromal interactions. However, androgen concentrations in the hypertrophic human prostate decrease significantly with age, suggesting an inverse correlation between androgen levels a...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920442/ https://www.ncbi.nlm.nih.gov/pubmed/29614830 http://dx.doi.org/10.3390/jcm7040068 |
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author | Ishii, Kenichiro Takahashi, Sanai Sugimura, Yoshiki Watanabe, Masatoshi |
author_facet | Ishii, Kenichiro Takahashi, Sanai Sugimura, Yoshiki Watanabe, Masatoshi |
author_sort | Ishii, Kenichiro |
collection | PubMed |
description | Androgens are essential for the development, differentiation, growth, and function of the prostate through epithelial–stromal interactions. However, androgen concentrations in the hypertrophic human prostate decrease significantly with age, suggesting an inverse correlation between androgen levels and proliferative diseases of the aging prostate. In elderly males, age- and/or androgen-related stromal remodeling is spontaneously induced, i.e., increased fibroblast and myofibroblast numbers, but decreased smooth muscle cell numbers in the prostatic stroma. These fibroblasts produce not only growth factors, cytokines, and extracellular matrix proteins, but also microRNAs as stromal paracrine signals that stimulate prostate epithelial cell proliferation. Surgical or chemical castration is the standard systemic therapy for patients with advanced prostate cancer. Androgen deprivation therapy induces temporary remission, but the majority of patients eventually progress to castration-resistant prostate cancer, which is associated with a high mortality rate. Androgen deprivation therapy-induced stromal remodeling may be involved in the development and progression of castration-resistant prostate cancer. In the tumor microenvironment, activated fibroblasts stimulating prostate cancer cell proliferation are called carcinoma-associated fibroblasts. In this review, we summarize the role of stromal paracrine signals in proliferative diseases of the aging human prostate and discuss the potential clinical applications of carcinoma-associated fibroblast-derived exosomal microRNAs as promising biomarkers. |
format | Online Article Text |
id | pubmed-5920442 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-59204422018-04-30 Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate Ishii, Kenichiro Takahashi, Sanai Sugimura, Yoshiki Watanabe, Masatoshi J Clin Med Review Androgens are essential for the development, differentiation, growth, and function of the prostate through epithelial–stromal interactions. However, androgen concentrations in the hypertrophic human prostate decrease significantly with age, suggesting an inverse correlation between androgen levels and proliferative diseases of the aging prostate. In elderly males, age- and/or androgen-related stromal remodeling is spontaneously induced, i.e., increased fibroblast and myofibroblast numbers, but decreased smooth muscle cell numbers in the prostatic stroma. These fibroblasts produce not only growth factors, cytokines, and extracellular matrix proteins, but also microRNAs as stromal paracrine signals that stimulate prostate epithelial cell proliferation. Surgical or chemical castration is the standard systemic therapy for patients with advanced prostate cancer. Androgen deprivation therapy induces temporary remission, but the majority of patients eventually progress to castration-resistant prostate cancer, which is associated with a high mortality rate. Androgen deprivation therapy-induced stromal remodeling may be involved in the development and progression of castration-resistant prostate cancer. In the tumor microenvironment, activated fibroblasts stimulating prostate cancer cell proliferation are called carcinoma-associated fibroblasts. In this review, we summarize the role of stromal paracrine signals in proliferative diseases of the aging human prostate and discuss the potential clinical applications of carcinoma-associated fibroblast-derived exosomal microRNAs as promising biomarkers. MDPI 2018-04-02 /pmc/articles/PMC5920442/ /pubmed/29614830 http://dx.doi.org/10.3390/jcm7040068 Text en © 2018 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Ishii, Kenichiro Takahashi, Sanai Sugimura, Yoshiki Watanabe, Masatoshi Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate |
title | Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate |
title_full | Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate |
title_fullStr | Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate |
title_full_unstemmed | Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate |
title_short | Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate |
title_sort | role of stromal paracrine signals in proliferative diseases of the aging human prostate |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920442/ https://www.ncbi.nlm.nih.gov/pubmed/29614830 http://dx.doi.org/10.3390/jcm7040068 |
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