title: Bladder cancer exosomes contain EDIL-3/Del1 and facilitate cancer progression.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Department of Urology, University of Rochester, Rochester, New York. Electronic address: Carla_beckham@urmc.rochester.edu.
authors: Carla J
authors: CJ
authors: Beckham
authors: Department of Genetics, University of Rochester, Rochester, New York.
authors: Jayme
authors: J
authors: Olsen
authors: Department of Urology, University of Rochester, Rochester, New York.
authors: Peng-Nien
authors: PN
authors: Yin
authors: Department of Urology, University of Rochester, Rochester, New York.
authors: Chia-Hao
authors: CH
authors: Wu
authors: Department of Biological Science and Technology, National University of Tainan, Taiwan, Republic of China.
authors: Huei-Ju
authors: HJ
authors: Ting
authors: Department of Biochemistry and Biophysics Proteomics Center, University of Rochester, Rochester, New York.
authors: Fred K
authors: FK
authors: Hagen
authors: Department of Urology, University of Rochester, Rochester, New York.
authors: Emelian
authors: E
authors: Scosyrev
authors: Department of Urology, University of Rochester, Rochester, New York.
authors: Edward M
authors: EM
authors: Messing
authors: Department of Urology, University of Rochester, Rochester, New York. Electronic address: yifen_lee@urmc.rochester.edu.
authors: Yi-Fen
authors: YF
authors: Lee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000032:analysis / Q000502:physiology*; D015815:Cell Adhesion Molecules; D018450:Disease Progression; D055354:Exosomes / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C110183:EDIL3 protein, human
keywords: EDIL-3 protein; disease progression; exosomes; human; urinary bladder; urinary bladder neoplasms