Identification of extracellular vesicle-borne periostin as a feature of muscle-invasive bladder cancer

Abstract

// Christopher R. Silvers 1 , Yu-Ru Liu 1 , Chia-Hao Wu 1 , Hiroshi Miyamoto 2 , Edward M. Messing 1 , Yi-Fen Lee 1 1 Department of Urology, University of Rochester Medical Center, Rochester, NY, USA 2 Departments of Pathology and Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Correspondence to: Yi-Fen Lee, e-mail: yifen_lee@urmc.rochester.edu Keywords: periostin, extracellular vesicle, exosome, muscle-invasive bladder cancer and biomarker Received: August 24, 2015      Accepted: February 25, 2016      Published: March 10, 2016 ABSTRACT Muscle-invasive bladder cancer (MIBC) is an aggressive malignancy with high mortality, and heterogeneity in MIBC results in variable clinical outcomes, posing challenges for clinical management. Extracellular vesicles (EVs) derived from MIBC have been shown to promote cancer progression. EVs derived from bladder cell lines were subjected to proteomic analysis, and periostin was chosen for further characterization due to its stage-specific gene expression profile. Knockdown of periostin by RNA interference reduces invasiveness in vitro and produces a rounder morphology. Importantly, treating low grade BC cells with periostin-rich EVs promotes cell aggressiveness and activates ERK oncogenic signals, and periostin suppression reverses these effects. These data suggest that MIBC might transfer periostin in an EV-mediated paracrine manner to promote the disease. To determine the potential of periostin as a bladder cancer indicator, patient urinary EVs were examined and found to have markedly higher levels of periostin than controls. In addition, immunohistochemical staining of a bladder cancer tissue microarray revealed that the presence of periostin in MIBC cells is correlated with worse prognosis. In conclusion, periostin is a component of bladder cancer cells associated with poor clinical outcome, and EVs can transfer oncogenic molecules such as periostin to affect the tumor environment and promote cancer progression.