You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology IV1 Apr 2017MP88-04 THE ADAPTOR PROTEIN CRK-INDUCED ERBB2 EXPRESSION PROMOTES TUMOR PROGRESSION AND METASTASIS OF BLADDER CANCER VIA EXOSOMES Kazuhiko Yoshida, Masumi Tsuda, Ryuji Matsumoto, Shingo Semba, Taichi Kimura, Mishie Tanino, Hiroshi Nishihara, Tsunenori Kondo, Kazunari Tanabe, and Shinya Tanaka Kazuhiko YoshidaKazuhiko Yoshida More articles by this author , Masumi TsudaMasumi Tsuda More articles by this author , Ryuji MatsumotoRyuji Matsumoto More articles by this author , Shingo SembaShingo Semba More articles by this author , Taichi KimuraTaichi Kimura More articles by this author , Mishie TaninoMishie Tanino More articles by this author , Hiroshi NishiharaHiroshi Nishihara More articles by this author , Tsunenori KondoTsunenori Kondo More articles by this author , Kazunari TanabeKazunari Tanabe More articles by this author , and Shinya TanakaShinya Tanaka More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2729AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Molecular targeted therapies have been developed for various cancers, however; which have not advanced beyond conventional chemotherapy for the locally advanced and metastatic bladder cancer (BC). Therefore, establishment of more efficient therapeutic strategy is urgently desired. Recently, extracellular exosomes are paid attention as important mediators of intercellular communication. Tumor-derived exosomes have known to transfer proteins and nucleic acids from the cells of origin to target cells and affect tumor progression and metastatic process. We have been reported that signaling adaptor protein CRK promotes cell growth, invasion, and adhesion in various cancers, however; the relationship between CRK and exosomes has remained unknown. Here, we investigated the effects of CRK-mediated exosomes on tumor progression and metastasis of BC. METHODS Human BC cell line UM-UC-3 were stably transfected with pCSII-CMV-tdTomato-Luc, and CRK was knocked-down by shRNA technique. The parental and CRK-depleted cells (CRKi) were orthotopically injected into nude mice, and the tumor progression and metastasis were investigated using IVIS Spectrum. In in vitro setting, expression levels of proteins associated with cell growth, survival, and invasion were examined in parental and CRKi UM-UC-3 cells and their exosomes, and the proteins contained in exosomes were identified by LC-TOF/MS. Low grade BC 5637 cells and HUVECs were treated with exosomes from parental UM-UC-3 cells, and the cell proliferation and invasion were analyzed. Furthermore, the metastases in mice pretreated with exosomes from parental and CRKi cells were investigated. RESULTS CRKi UM-UC-3 cells inhibited the tumor progression and metastasis in orthotopic xenograft models. We found that CRK and ErbB2 were contained in exosome from the parental UM-UC-3 cells, and the exosomes-incorporated-5637 and -HUVECs significantly promote the cell proliferation and invasion. In contrast, in exosomes from CRKi cells, the expression levels of ErbB2 were reduced, and the exosome-incorporated recipient cells decreased the growth and invasion. Of note, lung metastasis of UM-UC-3 cells was facilitated in mice educated by the parental UM-UC-3-derived exosomes, but not by CRKi cells-derived exosomes. CONCLUSIONS Here, we provide novel findings that CRK-regulated up-regulation of ErbB2 in the exosomes of BC facilitated the tumor progression and metastasis. Therefore, CRK and ErbB2 might be potent therapeutic targets to prevent the locally advanced and metastasis for BC patients. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1175 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Kazuhiko Yoshida More articles by this author Masumi Tsuda More articles by this author Ryuji Matsumoto More articles by this author Shingo Semba More articles by this author Taichi Kimura More articles by this author Mishie Tanino More articles by this author Hiroshi Nishihara More articles by this author Tsunenori Kondo More articles by this author Kazunari Tanabe More articles by this author Shinya Tanaka More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...