Increased Infiltrated Macrophages in Benign Prostatic Hyperplasia (BPH)

Wang, Xiaohai; Lin, Wen‐Jye; Izumi, Kouji; Jiang, Qi; Lai, Kuo-Pao; Xu, Defeng; Fang, Lei-Ya; Lu, Tianjing; Li, Lei; Xia, Shujie; Chang, Chawnshang

doi:10.1074/jbc.m112.355164

Cited by 66 publications

(37 citation statements)

References 46 publications

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“…38 Furthermore, macrophages may mediate epithelial-to-mesenchymal transition (EMT), which could further enhance the stromal compartment expansion. ASC-J9, a selective androgen receptor degradation enhancer, suppressed both stromal and epithelial cell growth without lowering serum androgen levels.…”

Section: Emerging Targets For Bph Therapymentioning

confidence: 99%

“…ASC-J9, a selective androgen receptor degradation enhancer, suppressed both stromal and epithelial cell growth without lowering serum androgen levels. 38, 39 In a mouse model of BPH induced by prolactin, ASC-J9 systemic therapy prevented BPH development. Moreover, the utility of ASC-J9, which does not alter serum testosterone or affect fertility, 40 is being investigated for treatment of prostate cancer, bladder cancer and liver cancer.…”

Section: Emerging Targets For Bph Therapymentioning

confidence: 99%

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Personalized Medicine for the Management of Benign Prostatic Hyperplasia

Bechis

Otsetov

et al. 2014

Journal of Urology

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Purpose Benign prostatic hyperplasia (BPH) affects over 50 percent of men by age 60 and is the cause of millions of dollars of healthcare expenditure for treatment of lower urinary tract symptoms (LUTS) and urinary obstruction. Despite the widespread use of medical therapy, there is no universal therapy that treats all men with symptomatic BPH, and at least 30% of patients do not respond to medical management and a subset require surgery. Significant advances have been made in understanding the natural history and development of the prostate, such as elucidating the role of the enzyme 5α reductase Type 2 (5AR2), and advances in genomics and biomarker discovery offer the potential for a more targeted approach to therapy. We review the current understanding of BPH progression as well as key genes and signaling pathways implicated in the process such as 5α reductase. We also explore the potential of biomarker screening and gene-specific therapies as tools to risk stratify BPH patients and identify those with symptomatic or medically resistant forms. Materials and Methods A PubMed® literature search of current and past peer-reviewed literature on prostate development, lower urinary tract symptoms, BPH pathogenesis, targeted therapy, biomarkers, epigenetics, 5AR2 and personalized medicine was performed. An additional Google Scholar™ search was conducted to broaden the scope of the review. Relevant reviews and original research articles were examined as well as their cited references, and a synopsis of original data was generated with the goal of informing the practicing urologist of these advances and their implications. Results BPH is associated with a state of hyperplasia of both the stromal and epithelial compartments, with 5AR2 and androgen signaling playing key roles in development and maintenance of the prostate. Chronic inflammation, multiple growth factor and hormonal signaling pathways, and medical comorbidities play an intricate role in prostate tissue homeostasis as well as its evolution into the clinical state of BPH. Resistance to medical therapy with finasteride may occur through silencing of the 5AR2 gene by DNA methylation, leading to a state in which 30% of adult prostates do not express 5AR2. Novel biomarkers such as single nucleotide polymorshisms may be used to risk stratify patients with symptomatic BPH and identify those at risk of progression or failure of medical therapy. Several inhibitors of the androgen receptor and other signaling pathways have recently been identified which appear to attenuate BPH progression and may offer alternative targets for medical therapy. Conclusions Progressive worsening of LUTS and bladder outlet obstruction secondary to BPH is the result of multiple pathways including androgen receptor signaling, pro-inflammatory cytokines and growth factor signals. New techniques in genomics, proteomics and epigenetics have led to the discovery of aberrant signaling pathways, novel biomarkers, DNA methylation signatures and potential gene-specific targets. As personaliz...

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Section: Emerging Targets For Bph Therapymentioning

confidence: 99%

Section: Emerging Targets For Bph Therapymentioning

confidence: 99%

Personalized Medicine for the Management of Benign Prostatic Hyperplasia

Bechis

Otsetov

et al. 2014

Journal of Urology

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“…A study investigating the interaction of infiltrated macrophages and stromal cells in BPH showed that mouse stromal cells (mPrSC) could recruit mouse macrophages (RAW264.7) that may result in promoting the proliferation of stromal cells [69]. Mechanism dissection found a significant increase of CCL3 expression in both mPrSC cells and RAW264.7 cells, and neutralizing CCL3 antibody could reduce the migration of RAW264.7 cells toward mPrSC cells and macrophage-enhanced mPrSC cell proliferation [69].…”

Section: Part I: Benign Prostatic Hyperplasiamentioning

confidence: 99%

“…Mechanism dissection found a significant increase of CCL3 expression in both mPrSC cells and RAW264.7 cells, and neutralizing CCL3 antibody could reduce the migration of RAW264.7 cells toward mPrSC cells and macrophage-enhanced mPrSC cell proliferation [69]. The in vivo Pb-PRL-tg mouse BPH model also confirmed the increased macrophages number and CCL3 expression in BPH and targeting stromal AR via deletion of the stromal fibromuscular AR in the Pb-PRL-tg mouse BPH model reduced the infiltrated macrophage number and CCL3 expression level in prostate.…”

Section: Part I: Benign Prostatic Hyperplasiamentioning

confidence: 99%

Androgen receptor and immune inflammation in benign prostatic hyperplasia and prostate cancer

Izumi

Chang

2014

Clinical Investigation

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Both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are frequent diseases in middle-aged to elderly men worldwide. While both diseases are linked to abnormal growth of the prostate, the epidemiological and pathological features of these two prostate diseases are different. BPH nodules typically arise from the transitional zone, and, in contrast, PCa arises from the peripheral zone. Androgen deprivation therapy alone may not be sufficient to cure these two prostatic diseases due to its undesirable side effects. The alteration of androgen receptor-mediated inflammatory signals from infiltrating immune cells and prostate stromal/epithelial cells may play key roles in those unwanted events. Herein, this review will focus on the roles of androgen/androgen receptor signals in the inflammation-induced progression of BPH and PCa.

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“…In our previous study, we used a BPH mouse model to elucidate a potential mechanism whereby macrophage infiltration promotes stromal cell proliferation in the prostate via the androgen receptor (AR)/inflammatory cytokine CCL3-dependent pathway, and this could be one potential mechanism for stromal expansion in the genesis and development of BPH (Wang et al, 2012[12]). …”

Section: Introductionmentioning

confidence: 99%