MP49-18 IDENTIFICATION OF EXTRACELLULAR VESICLE PERIOSTIN AS A URINARY BIOMARKER OF MUSCLE INVASIVE BLADDER CANCER (2015)

You have accessJournal of UrologyBladder Cancer: Basic Research III1 Apr 2015MP49-18 IDENTIFICATION OF EXTRACELLULAR VESICLE PERIOSTIN AS A URINARY BIOMARKER OF MUSCLE INVASIVE BLADDER CANCER Christopher Silvers, Miyamoto Hiroshi, Chia-Hao Wu, Edward Messing, and Yi-Fen Lee Christopher SilversChristopher Silvers More articles by this author , Miyamoto HiroshiMiyamoto Hiroshi More articles by this author , Chia-Hao WuChia-Hao Wu More articles by this author , Edward MessingEdward Messing More articles by this author , and Yi-Fen LeeYi-Fen Lee More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2813AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Periostin is an extracellular matrix protein with roles in cell adhesion and motility and is overexpressed in several cancer types. Multiple microarray dataset analyses of patient tissues have shown periostin mRNA to be overexpressed in muscle-invasive bladder cancer (MIBC), but further investigation has been limited. Extracellular vesicles (EV) are 30-2000 nm membrane-bound structures released by a variety of cell types and bearing a select cargo of proteins and nucleic acids. Our objectives were to investigate functions of periostin in MIBC, the contribution of EV-borne periostin, and the potential of EV periostin as a urinary marker METHODS Multiple bladder cancer cell lines were screened by quantitative real-time PCR (qPCR) for periostin expression. Two highly expressing lines (TCC-SUP and J82) were selected for periostin suppression by RNA interference (shPOSTN). Single clone knockdowns were assessed for changes in morphology, motility, invasiveness, and tumorigenicity in nude mice. EV were isolated and assayed for their ability to affect recipient cells' behaviors. Bladder cancer tissue microarray was performed and periostin expression levels in patients' tumors were correlated to to clinical outcomes. EV were isolated from the urine of MIBC patients and healthy controls, and periostin levels were assayed by Western blot. RESULTS J82 and TCC-SUP cells migrate and invade rapidly and have an extended morphology with long invadopodia. Periostin knockdown significantly slowed migration and invasion and produced a more circular morphology with fewer invadopodia. EV derived from shPOSTN cells had reduced ability to promote migration in recipient cells. Periostin expression in patient MIBC epithelial cells was negatively correlated with progression-free survival (P<0.021) and disease-specific survival (P<0.002). Ten MIBC (pT2-pT4) patient urine EV samples had markedly higher levels of periostin than stage pT1 disease samples (P<0.033), post-TURBT non-MIBC patients (P<0.004), or healthy volunteers (P<0.00003). CONCLUSIONS Periostin plays a heretofore unrecognized role in MIBC. Its expression in bladder cancer epithelial cells is related to the acquisition of an invasive phenotype and may be a promising therapeutic target, and the ability of EV containing high levels of periostin to influence recipient cells invites further study. The easy detectability of periostin in urine EV suggests its suitability as a biomarker of MIBC progression and a possible alternative to expensive cystoscopic surveillance © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e609-e610 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christopher Silvers More articles by this author Miyamoto Hiroshi More articles by this author Chia-Hao Wu More articles by this author Edward Messing More articles by this author Yi-Fen Lee More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...