MP17-18 PERI-PROSTATIC FAT (PPF) SECRETOME IN BPH PROGRESSION

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology1 Apr 2017MP17-18 PERI-PROSTATIC FAT (PPF) SECRETOME IN BPH PROGRESSION Omar Franco, Rodrigo Javier, Mathew Brady, Susan Crawford, and Simon Hayward Omar FrancoOmar Franco More articles by this author , Rodrigo JavierRodrigo Javier More articles by this author , Mathew BradyMathew Brady More articles by this author , Susan CrawfordSusan Crawford More articles by this author , and Simon HaywardSimon Hayward More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.607AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Periprostatic fat (PPF) is a well-vascularized adipose tissue that encloses the prostate containing resident adipose tissue macrophages (ATM) that are mobilized and recruited to areas with high tissue remodeling. PPF can secrete a wide range of adipokines involved in physiologic and pathologic processes. It is well established that the unbalanced production of pro-inflammatory adipokines is a key component to the development of the metabolic syndrome, a risk factor for lower urinary tract symptoms (LUTS) and BPH progression. However, the link between PPF and BPH pathogenesis has not been previously addressed. In this study, we hypothesize that during BPH progression, PPF secretes a pro-inflammatory cytokine profile leading to chronic activation of NF-κB signaling pathway METHODS PPF was collected from patients undergoing prostatectomy. The thickness of PPF was determined (distance between the pubic symphysis and prostate) in 205 patients using MRI and classified based on their BMI (lean vs. obese). The composition of PPF was characterized histopathologically with emphasis on the immune/inflammatory infiltrates. To determine the factors secreted by PPF, a short in vitro culture was used to generated conditioned medium and adipocytokine array analysis performed. Proliferation of benign prostate epithelial and stromal cells exposed to PPF-CM was assessed. Upon exposure to PPF-CM, activation of the NF-κB pathway was determined by western blot analysis. In vivo experiments were performed xenografting PPF and human prostate tissues under the kidney capsule of SCID mice to determine the effects of PPF on prostate histology and recruitment of inflammatory cells RESULTS Histological analysis of human PPF samples showed an increased ratio of multilocular/unilocular phenotype composed mainly of macrophages and mononuclear infiltrates in obese individuals compared to the unilocular pattern and lack of inflammatory infiltrates in lean patients. Obese patients showed a significantly increased PPF thickness (more than double) compared to lean patients. Interestingly MRI showed that PPF only partially surrounds the prostate in lean patients, while fat tissue almost completely encased the prostate in obese individuals. Adipokine array assays from PPF-CM samples show the expression of a profile of pro-inflammatory factors. Addition of androgens modulated the secretion of IL11, TGFβ1, IL16 and SDF1α, among oth CONCLUSIONS Our preliminary studies suggest a potential role for the PPF pro-inflammatory secretome in BPH pathogenesis © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e218 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Omar Franco More articles by this author Rodrigo Javier More articles by this author Mathew Brady More articles by this author Susan Crawford More articles by this author Simon Hayward More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...