Chemokines and BPH/LUTS

A wealth of published studies indicate that a variety of chemokines are actively secreted by the prostatic microenvironment consequent to disruptions in normal tissue homeostasis due to the aging process or inflammatory responses. The accumulation of senescent stromal fibroblasts, and, possibly, epithelial cells, may serve as potential driving forces behind chemokine secretion in the aging and enlarged human prostate. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and histological inflammation may also potentially serve as rich sources of chemokine secretion in the prostate. Once bound to their cognate receptors, chemokines can stimulate powerful pro-proliferation signal transduction pathways and thus function as potent growth factors in the development and progression of Benign Prostatic Hyperplasia (BPH) and lower urinary tract symptoms (LUTS). These functions have been amply demonstrated experimentally and particularly point to robust Mitogen Activated Protein Kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling, as well as global transcriptional responses, which mediate chemokine-stimulated cellular proliferative responses. A small body of literature also suggests that chemokine-mediated angiogenesis may comprise a contributing factor to BPH/LUTS development and progression. Thus, the observed low-level secretion of multiple chemokines within the aging prostatic microenvironment may promote a concomitant low-level, but cumulative, over-proliferation of both stromal fibroblastic and epithelial cell types associated with increased prostatic volume. Though the accumulated evidence is far from complete and suffers from some rather extensive gaps in knowledge, it argues favorably for the conclusion that chemokines can, and likely do, promote prostatic enlargement and the associated lower urinary tract symptoms, and justifies further investigations examining chemokines as potential therapeutic targets to delay or ablate BPH/LUTS initiation and progression. (C) 2011 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.