MP06-06 INCREASED EXPRESSION OF OSTEOPONTIN IN THE PROSTATE IS ASSOCIATED WITH THE CLINICAL PROGRESSION OF BPH

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (MP06)1 Apr 2020MP06-06 INCREASED EXPRESSION OF OSTEOPONTIN IN THE PROSTATE IS ASSOCIATED WITH THE CLINICAL PROGRESSION OF BPH Petra Popovics*, Wisam N. Awadallah, Sarah Kohrt, Thomas C. Case, Nicole L. Miller, Emily Ricke, Wei Huang, Marisol Ramirez-Solano, Qi Liu, Robert J. Matusik, William A. Ricke, and Magdalena M. Grabowska Petra Popovics*Petra Popovics* More articles by this author , Wisam N. AwadallahWisam N. Awadallah More articles by this author , Sarah KohrtSarah Kohrt More articles by this author , Thomas C. CaseThomas C. Case More articles by this author , Nicole L. MillerNicole L. Miller More articles by this author , Emily RickeEmily Ricke More articles by this author , Wei HuangWei Huang More articles by this author , Marisol Ramirez-SolanoMarisol Ramirez-Solano More articles by this author , Qi LiuQi Liu More articles by this author , Robert J. MatusikRobert J. Matusik More articles by this author , William A. RickeWilliam A. Ricke More articles by this author , and Magdalena M. GrabowskaMagdalena M. Grabowska More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000820.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Approximately 30% of men with lower urinary tract symptoms (LUTS) are resistant to medical therapies and progress to surgical intervention. The pathological changes producing LUTS include prostatic proliferation identified histologically as benign prostatic hyperplasia (BPH). Fibrogenic and inflammatory processes are also implicated in LUTS. Identification of new molecular pathways that provoke inflammatory responses and fibrosis, which are not targeted by current therapies, are vital to improve treatments of LUTS. Our study compared the expression of osteopontin (OPN), a pro-inflammatory and fibrotic molecule, in the prostate of patients with BPH characterized as incidental BPH, or as progressed to surgery. We also identified stimulatory signals contributing to the prostatic expression of OPN, as well as, genes that are activated in response to its elevated levels in vitro. METHODS: Immunohistochemistry was performed on prostate sections obtained from patients who had either undergone surgery to relieve LUTS (S-BPH, n=30) or had incidental BPH (I-BPH). I-BPH refers to specimens isolated from the transition zone of prostates after radical prostatectomy for low grade prostate cancer (n=8). Stained slides were captured with a Nuance Multispectral Imaging system and scored with inForm software. Protein level of OPN was determined by Western blot. The ability of prostate cells to secrete osteopontin in response to IL-1β and TGF-β1 and the expressional changes in genes regulated by OPN were determined in stromal (BHPrS-1) and epithelial (NHPrE-1) cell lines by ELISA and qPCR, respectively. RESULTS: The S-BPH group had significantly elevated H-score (p=0.0107, Mann-Whitney U test) and increased protein levels of OPN. OPN expression showed a widespread tissue distribution with a visibly higher level in glandular cells. We found that multiple splice variants of OPN are expressed in stromal and epithelial cells and its secretion is stimulated by TGF-β1 in NHPrE-1 and IL-1β and TGF-β1 in BHPrS-1 cells. Interestingly, we observed an increase in the expression of inflammatory genes in response to OPN including CXCL1, CXCL2, CXCL8, PTGS2 and IL6 in BHPrS-1, but this effect was not replicated in epithelial cell lines. CONCLUSIONS: Increased OPN levels are associated with the progression of BPH which appears to be related to inflammatory processes since OPN secretion by prostate cells is stimulated by cytokines. Pharmacological manipulation of prostatic OPN may have the potential to reduce LUTS by inhibiting inflammatory and fibrotic pathways. Source of Funding: NIDDK K12 DK100022 to PP, CWRU Start-up fund to MMG, 5R01 DK111554-03 to RJM, U54 DK104310 to WAR © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e53-e53 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Petra Popovics* More articles by this author Wisam N. Awadallah More articles by this author Sarah Kohrt More articles by this author Thomas C. Case More articles by this author Nicole L. Miller More articles by this author Emily Ricke More articles by this author Wei Huang More articles by this author Marisol Ramirez-Solano More articles by this author Qi Liu More articles by this author Robert J. Matusik More articles by this author William A. Ricke More articles by this author Magdalena M. Grabowska More articles by this author Expand All Advertisement PDF downloadLoading ...