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- W2024883517 abstract "No AccessJournal of UrologyInvestigative Urology1 Aug 2014Bladder Cancer Exosomes Contain EDIL-3/Del1 and Facilitate Cancer Progression Carla J. Beckham, Jayme Olsen, Peng-Nien Yin, Chia-Hao Wu, Huei-Ju Ting, Fred K. Hagen, Emelian Scosyrev, Edward M. Messing, and Yi-Fen Lee Carla J. BeckhamCarla J. Beckham Department of Urology, University of Rochester, Rochester, New York More articles by this author , Jayme OlsenJayme Olsen Department of Genetics, University of Rochester, Rochester, New York More articles by this author , Peng-Nien YinPeng-Nien Yin Department of Urology, University of Rochester, Rochester, New York More articles by this author , Chia-Hao WuChia-Hao Wu Department of Urology, University of Rochester, Rochester, New York More articles by this author , Huei-Ju TingHuei-Ju Ting Department of Biological Science and Technology, National University of Tainan, Taiwan, Republic of China More articles by this author , Fred K. HagenFred K. Hagen Department of Biochemistry and Biophysics Proteomics Center, University of Rochester, Rochester, New York More articles by this author , Emelian ScosyrevEmelian Scosyrev Department of Urology, University of Rochester, Rochester, New York More articles by this author , Edward M. MessingEdward M. Messing Department of Urology, University of Rochester, Rochester, New York More articles by this author , and Yi-Fen LeeYi-Fen Lee Department of Urology, University of Rochester, Rochester, New York More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.035AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: High grade bladder cancer is an extremely aggressive malignancy associated with high rates of morbidity and mortality. Understanding how exosomes may affect bladder cancer progression could reveal novel therapeutic targets. Materials and Methods: Exosomes derived from human bladder cancer cell lines and the urine of patients with high grade bladder cancer were assessed for the ability to promote cancer progression in standard assays. Exosomes purified from the high grade bladder cancer cell line TCC-SUP and the nonmalignant urothelial cell line SV-HUC were submitted for mass spectrometry analysis. EDIL-3 was identified and selected for further analysis. Western blot was done to determine EDIL-3 levels in urinary exosomes from patients with high grade bladder cancer. shRNA gene knockdown and recombinant EDIL-3 were applied to study EDIL-3 function. Results: Exosomes isolated from high grade bladder cancer cells and the urine of patients with high grade bladder cancer promoted angiogenesis and migration of bladder cancer cells and endothelial cells. We silenced EDIL-3 expression and found that shEDIL-3 exosomes did not facilitate angiogenesis, and urothelial and endothelial cell migration. Moreover, exosomes purified from the urine of patients with high grade bladder cancer contained significantly higher EDIL-3 levels than exosomes from the urine of healthy controls. EDIL-3 activated epidermal growth factor receptor signaling while blockade of epidermal growth factor receptor signaling abrogated this EDIL-3 induced bladder cell migration. Conclusions: Exosomes derived from the urine of patients with bladder cancer contains bioactive molecules such as EDIL-3. Identifying these components and their associated oncogenic pathways could lead to novel therapeutic targets and treatment strategies. References 1 : Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int2010; 78: 838. Google Scholar 2 : Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol2008; 10: 1470. Google Scholar 3 : Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. 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Google Scholar © 2014 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byAtala A (2019) Re: Bladder Cancer Extracellular Vesicles Drive Tumorigenesis by Inducing the Unfolded Protein Response in Endoplasmic Reticulum of Nonmalignant CellsJournal of Urology, VOL. 202, NO. 6, (1100-1101), Online publication date: 1-Dec-2019.Franzen C, Blackwell R, Foreman K, Kuo P, Flanigan R and Gupta G (2018) Urinary Exosomes: The Potential for Biomarker Utility, Intercellular Signaling and Therapeutics in Urological MalignancyJournal of Urology, VOL. 195, NO. 5, (1331-1339), Online publication date: 1-May-2016.Andersson K (2018) This Month in Investigative UrologyJournal of Urology, VOL. 192, NO. 2, (295-296), Online publication date: 1-Aug-2014.Street J, Yuen P and Star R (2018) Bioactive Exosomes: Possibilities for Diagnosis and Management of Bladder CancerJournal of Urology, VOL. 192, NO. 2, (297-298), Online publication date: 1-Aug-2014. Volume 192Issue 2August 2014Page: 583-592Supplementary Materials Advertisement Copyright & Permissions© 2014 by American Urological Association Education and Research, Inc.Keywordsurinary bladderhumandisease progressionexosomesEDIL-3 proteinurinary bladder neoplasmsAcknowledgmentsDr. Reznikoff provided SV-HUC cells. The Berk Laboratory, University of Rochester provided HUVECs. C.R. Silvers provided technical assistance. M. Sowden and S. Majumder, CVRI, provided HUVEC cells and protocols. Jonathan Flax provided insight. Roy R. Parker read the manuscript and provided editorial advice. L. Maquat read the manuscript and provided insight into experiments. H. Miyamoto made pathological diagnoses and read slides. K. Bentley, Electron Microscopy Research Core, provided assistance. B. Smith and S. Schoen assisted with institutional review board materials. M. Kiernan enrolled patients.MetricsAuthor Information Carla J. Beckham Department of Urology, University of Rochester, Rochester, New York More articles by this author Jayme Olsen Department of Genetics, University of Rochester, Rochester, New York More articles by this author Peng-Nien Yin Department of Urology, University of Rochester, Rochester, New York More articles by this author Chia-Hao Wu Department of Urology, University of Rochester, Rochester, New York More articles by this author Huei-Ju Ting Department of Biological Science and Technology, National University of Tainan, Taiwan, Republic of China More articles by this author Fred K. Hagen Department of Biochemistry and Biophysics Proteomics Center, University of Rochester, Rochester, New York More articles by this author Emelian Scosyrev Department of Urology, University of Rochester, Rochester, New York More articles by this author Edward M. Messing Department of Urology, University of Rochester, Rochester, New York More articles by this author Yi-Fen Lee Department of Urology, University of Rochester, Rochester, New York More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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