The use of the 5-alpha reductase inhibitors (5-ARIs) finasteride and dutasteride for prostate cancer prevention is still under debate. The FDA recently concluded that the increased prevalence of high-grade tumors among 5-ARI-treated patients must not be neglected, and they decided to disallow the use of 5-ARIs for prostate cancer prevention. This study was conducted to verify the effects of finasteride on prostate cell migration and invasion and the related enzymes/proteins in normal human and tumoral prostatic cell lines. RWPE-1, LNCaP, PC3 and DU145 cells were cultivated to 60% confluence and exposed for different periods to either 10 µM or 50 µM finasteride that was diluted in culture medium. The conditioned media were collected and concentrated, and MMP2 and MMP9 activities and TIMP-1 and TIMP-2 protein expression were determined. Cell viability, migration and invasion were analyzed, and the remaining cell extracts were submitted to androgen receptor (AR) detection by western blotting techniques. Experiments were carried out in triplicate. Cell viability was not significantly affected by finasteride exposure. Finasteride significantly downregulated MMP2 and MMP9 activities in RWPE-1 and PC3 cells and MMP2 in DU145 cells. TIMP-2 expression in RWPE-1 cells was upregulated after exposure. The cell invasion of all four tested cell lines was inhibited by exposure to 50 µM of finasteride, and migration inhibition only occurred for RWPE-1 and LNCaP cells. AR was expressed by LNCaP, RWPE-1 and PC3 cells. Although the debate on the higher incidence of high-grade prostate cancer among 5-ARI-treated patients remains, our findings indicate that finasteride may attenuate tumor aggressiveness and invasion, which could vary depending on the androgen responsiveness of a patient’s prostate cells.

Evidence is emerging that highlights the far-reaching consequences of a high-fat diet (HFD) on kidney morphology and function disorders. The present study was performed on 3-, 5-, 7- and 9-week-old HFD female rats compared with the appropriate gender and age-matched animals. We evaluated the kidney expression of angiotensin type II receptor and fibrotic and epithelial-to-mesenchymal transition (EMT) markers, by immunoblotting and immunohistochemical and histological techniques, in parallel with kidney function. In the current study, the time-course HFD-treated group showed, by immunoblotting and immunohistochemical analysis, an early time-course increase in the expression of transforming growth factor β-1 (TGFβ-1) in the entire kidney of HFD-treated rats, compared with that observed in the control group. Simultaneously, the study shows a transient increase in the expression of ZEB2 in the HFD whole kidney accompanied by a fall in the E-cadherin expression and increased collagen and fibronectin deposition. A pronounced decrease in fractional urinary sodium excretion was also demonstrated in the long-term HFD-treated rats. The decreased FE_Na⁺ was accompanied by a fall in FEP_Na⁺ and FEPP_Na⁺, which occurred in association with significantly decreased C_Cr and, certainly on the sodium-filtered load. The reduction in the glomerular filtration rate (GFR) occurred in parallel to proteinuria and glomerular desmin overexpression. The results of the current study suggest that podocyte injury in parallel with observed proteinuria and evidence of EMT transformation are associated with long-term loss of kidney function and renal sodium and water retention.

Prostate cancer (PCa) is the leading cause of cancer-associated mortality in men, and new biomarkers are still needed. The expression pattern and protein tissue localization of proteoglycans of the syndecan family (SDC 1–4) and syntenin-1 (SDCBP) were determined in normal and prostatic tumor tissue from two genetically engineered mouse models and human prostate tumors. Studies were validated using SDC 1–4 and SDCBP mRNA levels and patient survival data from The Cancer Genome Atlas and CamCAP databases. RNAseq showed increased expression of Sdc1 in Pb-Cre4/Pten^f/f mouse Pca and upregulation of Sdc3 expression and downregulation of Sdc2 and Sdc4 when compared to the normal prostatic tissue in Pb-Cre4/Trp53^f/f-;Rb1^f/f mouse tumors. These changes were confirmed by immunohistochemistry. In human PCa, SDC 1–4 and SDCBP immunostaining showed variable localization. Furthermore, Kaplan–Meier analysis showed that patients expressing SDC3 had shorter prostate-specific survival than those without SDC3 expression (log-rank test, p = 0.0047). Analysis of the MSKCC-derived expression showed that SDC1 and SDC3 overexpression is predictive of decreased biochemical recurrence-free survival (p = 0.0099 and p = 0.045, respectively), and SDC4 overexpression is predictive of increased biochemical recurrence-free survival (p = 0.035). SDC4 overexpression was associated with a better prognosis, while SDC1 and SDC3 were associated with more aggressive tumors and a worse prognosis.

Summary: Matrix metalloproteinses (MMPs) are enzymes involved in prostatic development, growth, disease‐induced tissue remodelling and secretory fluid. Although the prostate function depends upon androgen regulation, the relationship between MMPs and androgen has not been well established. Here, we evaluated MMP‐2 and MMP‐9 gelatinolytic activity in association with tissue localization during ventral prostate atrophy and regrowth induced by testosterone replacement (TR). Adult male Wistar rats were divided into three experimental groups: control, castrated (CS) and TR 21 days after castration. Ventral prostate (VP) was excised at 3, 5, 7 and 21 days after castration in CS group, and at 3, 5, 7 and 10 days after TR (4 mg/kg/day) in TR group. The VP was dissected, weighed and processed for histology, immunohistochemistry, ultrastructure and zymography analyses. Castration elicited the typical parenchymal atrophy and stromal condensation. TR induced intense epithelial growth towards the stromal space to restore the prostate histoarchitecture. MMP‐2 and MMP‐9 immunostaining presented intense reaction in CS and TR groups, mainly in the epithelial and endothelial cells. After TR, a strong immunoreaction for MMP‐2 was observed in the activated stromal fibroblasts. Zymography showed that MMP‐2 and MMP‐9 activity, mainly the active form, increased after castration. In contrast, TR induced an additional increase in MMP‐2 activity, but not in MMP‐9. In conclusion, the overall behaviour of MMP‐2 and MMP‐9 within the prostate under androgen handling is highly complex, as each glandular compartment and cell type is affected differently by the androgenic status. Prostate regrowth appears to involve a more effective participation of MMP‐2 in both epithelial and stromal compartments, while MMP‐9 plays a major role in the late prostate atrophy and early regrowth.