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J. Clin. Med. 2018, 7(4), 68; https://doi.org/10.3390/jcm7040068

Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate

1
Department of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
2
Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
3
Laboratory for Medical Engineering, Division of Materials Science and Chemical Engineering, Graduate School of Engineering, Yokohama National University, Yokohama, Kanagawa 240-8501, Japan
*
Author to whom correspondence should be addressed.
Received: 13 March 2018 / Revised: 28 March 2018 / Accepted: 28 March 2018 / Published: 2 April 2018
(This article belongs to the Section Molecular Medicine)
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Abstract

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. View Full-Text
Keywords: proliferative diseases of the aging human prostate; epithelial–stromal interactions; stromal remodeling; stromal paracrine signals; carcinoma-associated fibroblast-derived exosomal microRNAs proliferative diseases of the aging human prostate; epithelial–stromal interactions; stromal remodeling; stromal paracrine signals; carcinoma-associated fibroblast-derived exosomal microRNAs
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Ishii, K.; Takahashi, S.; Sugimura, Y.; Watanabe, M. Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate. J. Clin. Med. 2018, 7, 68.

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