Invited ReviewThe functional role of reactive stroma in benign prostatic hyperplasia☆
Section snippets
Benign prostatic hyperplasia and the reactive phenotype
The human prostate gland is composed of secretory epithelium arranged in glandular acini within a fibromuscular stroma composed primarily of smooth muscle. The stromal compartment also contains fibroblasts, vasculature, nerves and immune components. In an interactive manner, each of these epithelial and stromal components is likely involved in the genesis and evolution of benign prostatic hyperplasia (BPH). Understanding prostate gland development is helpful for interpreting some of the
Epithelial barrier function and the reactive stroma response
Epithelia, though specialized for unique functions throughout the body, share several common morphological features. In general, epithelia line a given surface, directly apposed one to another, yielding a layer. Epithelial tight junctions and other junctional complexes allow for a tight and fairly robust structural integrity of this epithelial lining layer, thus protecting against frictional expansion and contraction within dynamic exocrine organs, such as the prostate. Moreover, the apical
Reactive stroma repair and myofibroblasts
Although the mechanisms of genesis and/or recruitment of myofibroblasts to diseased tissue regions are as yet unresolved (Phan, 2008), myofibroblasts play a central role in fibrotic diseases of the skin, liver, pancreas, kidney and urogenital tissues, among others. Myofibroblasts exhibit properties of both smooth muscle cells and fibroblasts, secreting a host of growth factors and chemokines (Powell et al., 1999), and are defined here histologically as co-expressing vimentin, smooth muscle α
Benign prostatic hyperplasia and chronic inflammation
At present, there is no consensus on the etiology of BPH. There have been many suggestions, some mechanical in nature, such as altered urodynamic function due to increased prostatic urethral angulation (Cho et al., 2008). Some have identified potential molecular events gone awry, such as elevated oxidative stress (Gradini et al., 1999, Aryal et al., 2007), ischemic damage due to vascular impairment (Berger et al., 2005), loss of negative regulators of cell cycle control (Cordon-Cardo et al.,
Chemokines and cytokines in BPH reactive stroma
Many chemokines and cytokines have been shown to be associated with BPH. The CXC chemokines shown to be specifically associated with BPH include IL-1α (Giri and Ittmann, 2000), IL-2 (Royuela et al., 2000), IL-8 (Penna et al., 2007, Castro et al., 2004), IL-15 and IL-17 (Handisurya et al., 2001, Steiner et al., 2002). Among these, IL-8 was shown to be expressed specifically in BPH epithelial cells, and to stimulate expression of fibroblast growth factor 2 (FGF2) in vitro (Castro et al., 2004,
Interleukin-8 and benign prostatic hyperplasia
Interleukins, in general, are mediators of inflammatory processes and are central to induction of wound repair responses and have been implicated in fibrosis. In the prostate gland, IL-8, IL-1α and IL-6 have each gained attention. Overexpression of IL-8 is universally observed in many proliferative disorders and sites of inflammation. IL-8 is a multifunctional chemokine interleukin that regulates many immune host responses and wound repair mechanisms. The elevated expression of several
Extracellular matrix in reactive stroma and BPH
Tenascin-C is an extracellular matrix glycoprotein that exhibits altered expression and deposition patterns in human BPH. We have shown that this is statistically correlated with elevated epithelial expression of IL-8 (Schauer et al., 2008). Moreover, tenascin-C is deposited in activated fibroblasts/myofibroblasts immediately adjacent to BPH epithelial acini. These cells have a phenotype very similar to what we have reported for reactive stroma in prostate cancer. Reactive stroma consisting of
Summary and conclusions
The etiology and specific mechanisms that lead to phenotypic changes that manifest as benign prostate disease remain poorly understood. Recent data suggest that pathophysiological signaling mechanisms are complex, likely involving age-related and chronic defects in tissue homeostasis that lead to compensatory and reactive changes in both the stroma and the epithelial tissue compartments. The historical perspective of BPH biology suggests that the compensatory biology likely involves
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2021, Asian Journal of UrologyCitation Excerpt :Thus, the independent association of the cytokine solely with prostate volume is difficult to be proven significant as seen in the results of the study. Physiologically, unlike other organs the prostate keeps growing throughout the adult male life [41]. An ample amount of studies in the past have explored the role of testosterone in the increase of prostate volume.
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Funding Sources: Supported by NIH Grants R01 DK083293 and R01 CA58093.