scholarly journals Androgen Receptor Expression in Epithelial and Stromal Cells of Prostatic Carcinoma and Benign Prostatic Hyperplasia

2017 ◽  
Vol 5 (5) ◽  
pp. 608-612
Author(s):  
Vanja Filipovski ◽  
Katerina Kubelka-Sabit ◽  
Dzengis Jasar ◽  
Vesna Janevska
Keyword(s):  
Androgen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
Epithelial Cells ◽  
Stromal Cells ◽  
Prostatic Carcinoma ◽  
Growth Control ◽  
Prostatic Hyperplasia ◽  
Receptor Expression ◽  
Stromal Microenvironment ◽  
Histological Score

BACKGROUND: Prostatic carcinoma (PCa) derives from prostatic epithelial cells. However stromal microenvironment, associated with malignant epithelium, also plays a role in prostatic carcinogenesis. Alterations in prostatic stromal cells contribute to the loss of growth control in epithelial cells that lead to progression of PCa.AIM: To analyse the differences between Androgen Receptor (AR) expression in both epithelial and stromal cells in PCa and the surrounding benign prostatic hyperplasia (BPH) and to compare the results with tumour grade.MATERIAL AND METHODS: Samples from 70 cases of radical prostatectomy specimens were used. The expression and intensity of the signal for AR was analysed in the epithelial and stromal cells of PCa and BPH, and the data was quantified using histological score (H-score).RESULTS: AR showed significantly lower expression in both epithelial and stromal cells of PCa compared to BPH. In PCa a significant positive correlation of AR expression was found between stromal and epithelial cells of PCa. AR expression showed a correlation between the stromal cells of PCa and tumour grade.CONCLUSION: AR expression is reduced in epithelial and stromal cells of PCa. Expression of AR in stromal cells of PCa significantly correlates with tumour grade.

scholarly journals Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

2012 ◽  
Vol 214 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Linda Vignozzi ◽  
Ilaria Cellai ◽  
Raffaella Santi ◽  
Letizia Lombardelli ◽  
Annamaria Morelli ◽  
...  
Keyword(s):  
T Cells ◽  
Growth Factors ◽  
Androgen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
Stromal Cells ◽  
Receptor Activation ◽  
Prostatic Hyperplasia ◽  
Serum Testosterone Level ◽  
Antiinflammatory Effect ◽  
Inflammatory Growth

Progression of benign prostatic hyperplasia (BPH) involves chronic inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate inflammation and tissue remodeling are exacerbated by hypogonadism and prevented by testosterone supplementation. We now investigated whether, in humans, hypogonadism was associated with more severe BPH inflammation and the in vitro effect of the selective androgen receptor agonist dihydrotestosterone (DHT) on cultures of stromal cells derived from BPH patients (hBPH). Histological analysis of inflammatory infiltrates in prostatectomy specimens from a cohort of BPH patients and correlation with serum testosterone level was performed. Even after adjusting for confounding factors, hypogonadism was associated with a fivefold increased risk of intraprostatic inflammation, which was also more severe than that observed in eugonadal BPH patients. Triggering hBPH cells by inflammatory stimuli (tumor necrosis factor α, lipopolysaccharide, or CD4+T cells) induced abundant secretion of inflammatory/growth factors (interleukin 6 (IL6), IL8, and basic fibroblast growth factor (bFGF)). Co-culture of CD4+T cells with hBPH cells induced secretion of Th1 inducer (IL12), Th1-recruiting chemokine (interferon γ inducible protein 10, IP10), and Th2 (IL9)- and Th17 (IL17)-specific cytokines. Pretreatment with DHT inhibited NF-κB activation and suppressed secretion of several inflammatory/growth factors, with the most pronounced effects on IL8, IL6, and bFGF. Reduced inflammatory cytokine production by testosterone cells, an increase in IL10, and a significant reduction of testosterone cells proliferation suggested that DHT exerted a broad antiinflammatory effect on testosterone cells. In conclusion, our data demonstrate that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses.

Characterization and Measurement of the Androgen Receptor in Human Benign Prostatic Hyperplasia and Prostatic Carcinoma

1977 ◽  
Vol 45 (5) ◽  
pp. 920-930 ◽  
Author(s):  
MAREK SNOCHOWSKI ◽  
ÅKE POUSETTE ◽  
PETER EKMAN ◽  
DOMINIQUE BRESSION ◽  
LENNART ANDERSSON ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
Prostatic Carcinoma ◽  
Prostatic Hyperplasia

scholarly journals Targeting Androgen Receptor to Suppress Macrophage-induced EMT and Benign Prostatic Hyperplasia (BPH) Development

2012 ◽  
Vol 26 (10) ◽  
pp. 1707-1715 ◽  
Author(s):  
Tianjing Lu ◽  
Wen-Jye Lin ◽  
Kouji Izumi ◽  
Xiaohai Wang ◽  
Defeng Xu ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Prostatic Hyperplasia ◽  
Sphere Diameter ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Prostate Epithelial Cells ◽  
Emt Markers

Abstract Early studies suggested macrophages might play roles in inflammation-associated benign prostatic hyperplasia (BPH) development, yet the underlying mechanisms remain unclear. Here we first showed that CD68+ macrophages were identified in both epithelium and the stromal area of human BPH tissues. We then established an in vitro co-culture model with prostate epithelial and macrophage cell lines to study the potential impacts of infiltrating macrophages in the BPH development and found that co-culturing prostate epithelial cells with macrophages promoted migration of macrophages. In a three-dimensional culture system, the sphere diameter of BPH-1 prostate cells was significantly increased during coculture with THP-1 macrophage cells. Mechanism dissection suggested that expression levels of epithelial-mesenchymal transition (EMT) markers, such as N-cadherin, Snail, and TGF-β2, were increased, and administration of anti-TGF-β2 neutralizing antibody during co-culture suppressed the EMT and THP-1-mediated growth of BPH-1 cells, suggesting THP-1 might go through EMT to influence the BPH development and progression. Importantly, we found that modulation of androgen receptor (AR) in BPH-1 and mPrE cells significantly increased THP-1 and RAW264.7 cell migration, respectively, and enhanced expression levels of EMT markers, suggesting that AR in prostate epithelial cells might play a role in promoting macrophage-mediated EMT in prostate epithelial cells. Silencing AR function via an AR degradation enhancer, ASC-J9, decreased the macrophage migration to BPH-1 cells and suppressed EMT marker expression. Together, these results provide the first evidence to demonstrate that prostate epithelial AR function is important for macrophage-mediated EMT and proliferation of prostate epithelial cells, which represents a previously unrecognized role of AR in the cross-talk between macrophages and prostate epithelial cells. These results may provide new insights for a new therapeutic approach to battle BPH via targeting AR and AR-mediated inflammatory signaling pathways.

scholarly journals Stereological analysis of androgen receptors in prostate cancer and benign prostatic hyperplasia

2018 ◽  
Vol 71 (3-4) ◽  
pp. 89-95
Author(s):  
Sandra Trivunic-Dajko ◽  
Jovo Bogdanovic ◽  
Sasa Vojinov ◽  
Andrejic Visnjic
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
Prostatic Cancer ◽  
Androgen Receptors ◽  
Immunohistochemical Analysis ◽  
Prostatic Hyperplasia ◽  
Receptor Expression ◽  
Androgen Receptor Expression ◽  
Stereological Analysis

Introduction. Through androgen receptors, androgens regulate prostate cellular growth and function, proliferation, differentiation, apoptosis, lipid metabolism and secretory activity, as well as development and progression of prostate cancer. Prostate cancer, and its primary glandular tissue are influenced by hormones, and it is used for therapeutic purposes. Anti-androgen treatment is carried out in patients with metastatic prostatic cancer, in order to block effects of androgens. Immunohistochemical analysis of androgen receptors in the prostate cancer tissue may help us to assume how the tumors will react to the anti-androgen therapy, if they are androgen-positive, -negative, or hormone resistant tumors. Knowledge of the presence of androgen receptors in the tumor tissue may be a prognostic indicator in histopathological analysis. The aim of this study was stereological evaluation of androgen receptor expression in patients with benign prostatic hyperplasia and in patients with prostatic cancer, before therapy. Material and Methods. Immunohistochemical analysis was carried out using anti-human androgen receptor monoclonal antibody 441. The presence and intensity of the androgen receptors were evaluated in 195 patients: 165 with benign prostatic hyperplasia and 30 with prostatic cancer using Weibel?s multi-purpose M 42 stereological test system. Material was obtained by needle biopsy or transurethral resection of the prostate. Results. All secretory cells in patients with benign prostatic hyperplasia were androgen positive, while in patients with prostatic cancer, all tumors were mostly androgen positive, some with foci of negativity. The resulting negative correlation with Gleason score and International Society of Urological Pathology grade was not statistically significant. Conclusion. Study results of stereological analysis of androgen receptors indicate that prior the therapy prostate cancer is androgendependent, with a high level of androgen receptor expression, although slightly lower compared to benign prostatic hyperplasia.

scholarly journals Prostatic osteopontin expression is associated with symptomatic benign prostatic hyperplasia

2019 ◽  
Author(s):  
Petra Popovics ◽  
Wisam N. Awadallah ◽  
Sarah Kohrt ◽  
Thomas C. Case ◽  
Nicole L. Miller ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Epithelial Cells ◽  
Stromal Cells ◽  
Multispectral Imaging ◽  
Imaging System ◽  
Staining Intensity ◽  
Prostatic Hyperplasia ◽  
Low Grade ◽  
Symptomatic Benign Prostatic Hyperplasia ◽  
Tgf Β1

AbstractBackgroundMale lower urinary tract symptoms (LUTS) occur in more than half of men above 50 years of age. LUTS were traditionally attributed to benign prostatic hyperplasia (BPH) and therefore the clinical terminology often use LUTS and BPH interchangeably. More recently, LUTS were also linked to fibrogenic and inflammatory processes. We tested whether osteopontin (OPN), a pro-inflammatory and pro-fibrotic molecule, is increased in symptomatic BPH. We also tested whether prostate epithelial and stromal cells secrete OPN in response to pro-inflammatory stimuli and identified downstream targets of OPN in prostate stromal cells.MethodsImmunohistochemistry was performed on prostate sections obtained from the transition zone (TZ) of patients who underwent surgery (Holmium laser enucleation of the prostate) to relieve LUTS i.e. surgical BPH (S-BPH) or patients who underwent radical prostatectomy to remove low-grade prostate cancer (incidental BPH, I-BPH). Images of stained tissue sections were captured with a Nuance Multispectral Imaging system and histoscore, as a measure of OPN staining intensity, was determined with inForm software. OPN protein abundance was determined by Western blot. The ability of prostate cells to secrete osteopontin in response to IL-1β and TGF-β1 was determined in stromal (BHPrS-1) and epithelial (NHPrE-1 and BHPrE-1) cells by ELISA. qPCR was used to measure gene expression changes in these cells in response to OPN.ResultsOPN immunostaining (p=0.0107) and protein levels were more abundant in S-BPH than I-BPH. Staining was distributed across all cell types with highest levels in epithelial cells. Multiple OPN protein variants were identified in immortalized prostate stromal and epithelial cells. TGF-β1 stimulated OPN secretion by NHPrE-1 cells and both IL-1β and TGF-β1 stimulated OPN secretion by BHPrS-1 cells. Interestingly, recombinant OPN increased the mRNA expression of CXCL1, CXCL2, CXCL8, PTGS2 and IL6 in BHPrS-1, but not in epithelial cell lines.ConclusionsOPN is more abundant in prostates of men with S-BPH compared to men with I-BPH. OPN secretion is stimulated by pro-inflammatory cytokines, and OPN acts directly on stromal cells to drive the synthesis of pro-inflammatory mRNAs. Pharmacological manipulation of prostatic OPN may have the potential to reduce LUTS by inhibiting both inflammatory and fibrotic pathways.

Sign in / Sign up

Export Citation Format

Share Document