You have accessJournal of UrologyBladder Cancer: Basic Research II1 Apr 2014MP28-05 EXOSOMES PROMOTE BLADDER CELL MALIGNANT TRANSFORMATION, A NEW MECHANISM FOR THE FILED EFFECT Chia-Hao Wu, Christopher Silvers, Christopher Silvers, Edward Messing, and Yi-Fen Lee Chia-Hao WuChia-Hao Wu More articles by this author , Christopher SilversChristopher Silvers More articles by this author , Christopher SilversChristopher Silvers 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.2014.02.654AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Greater than 70% of newly diagnosed bladder cancers are non-muscle invasive and these tumors tend to recur throughout the bladder lining and are not strictly limited to previous sites of resection, suggesting that the entire bladder is made permissive for tumorigenesis. This phenomenon has been termed field effect change (FEC), and the contributing factors driving this FEC are not clear. Exosomes are small membrane vesicles ranging from 30 to 100 nm. They are secreted from numerous types of cells into the extracellular milieu and can be taken up by neighboring cells, which act as novel intercellular modes of communication. To reveal exosomes¡¦ roles in bladder tumorigenesis, we conducted a series of laboratory experiments. METHODS Immortalized bladder cells, SV-HUC, were used as a model system to evaluate exosome-induced cellular transformation. Exosomes were purified from high-grade bladder cancer cells, TCC-SUP and SV-HUC cells, following a series of steps of centrifugation. We screened the exosome intake inhibitors via monitoring PKH67-labeling exosomes internalization. The tumorigenicity was determined by soft agar assay and further confirmed by xenografted nude mice. DNA damages and cellular senescence, as the results of exosome-induced oncogenic insults, were determined by gamma-H2Ax and senescence-associated beta-gal stainings. The genes involving in the DNA damage response, tumor suppressive function and oncogenic pathways were examined by real-time quantification PCR. RESULTS Long-term exposure of SV-HUC to exosome- enriched environment induced SV-HUC malignant transformation, where exosome-treated cells gain anchorage-independent growth by soft agar assay, and PBS-treated cells did not. The tumorigenicity was confirmed in vivo by the xenografted nude mice model. In addition, these transformed SV-HUC cells also gain the function of mobility and invasiveness. Importantly, dynasore, the inhibitor that blocks exosome intake, reversed the exosome-induced SV-HUC malignant transformation. Genes that are involved in DNA damage response and tumor suppressive function were found to be reduced, and several oncogenes were elevated in the transformed SV-HUC cells as compared to parental SV-HUC cells. CONCLUSIONS These data, for the first time, demonstrate that exosomes play a role in the early stage of neoplasmic transformation and provide a novel mechanism to explain FEC. More importantly, deprivation of exosome intake resulted in diminished SV-HUC malignant transformation revealing the therapeutic potential of dynasore. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e297-e298 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Chia-Hao Wu More articles by this author Christopher Silvers More articles by this author Christopher Silvers 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 ...