title: Human agonistic antibody to tumor necrosis factor-related apoptosis-inducing ligand receptor 2 induces cytotoxicity and apoptosis in prostate cancer and bladder cancer cells.
abstract: OBJECTIVE
  Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of tumor cells through two of its receptors: TRAIL-R1 and TRAIL-R2. In this study, we investigated the susceptibility of human prostate cancer and bladder cancer cells to HGS-ETR2, a human monoclonal agonistic antibody specific for TRAIL-R2.
  
  
  METHODS
  The cell surface expression of TRAIL-R1 and TRAIL-R2 on prostate cancer and bladder cancer cells was determined using flow cytometry. Cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and caspase activities were measured by a quantitative colorimetric assay.
  
  
  RESULTS
  HGS-ETR2 effectively induced apoptotic cell death in DU145, PC3, and LNCaP human prostate cancer cells and J82 and T24 human bladder cancer cells. The increased effectiveness of HGS-ETR2 for inducing cell death might have been affected by differences in the cell surface expression of the two TRAIL receptors, in that TRAIL-R2, but not TRAIL-R1, was frequently expressed in the prostate cancer and bladder cancer cells. HGS-ETR2 significantly activated the caspase cascade, including caspase-3, -6, -8, and -9, which were the downstream molecules of the death receptors in prostate cancer cells. Caspase-3, -6, and -9 were also significantly activated with HGS-ETR2-induced apoptosis in the bladder cancer cells.
  
  
  CONCLUSIONS
  These findings suggest the potential utility of TRAIL-R2 antibody as a novel therapeutic agent against prostate cancer and bladder cancer.
authors.affiliation: Department of Urology, Kagawa University Faculty of Medicine, Kagawa, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Shimada
authors.forename: Xiuxian
authors.initials: X
authors.lastname: Wu
authors.forename: Xinghua
authors.initials: X
authors.lastname: Jin
authors.forename: Mohammed Ahmed Abdel-Muneem
authors.initials: MA
authors.lastname: Nouh
authors.forename: Michele
authors.initials: M
authors.lastname: Fiscella
authors.forename: Vivian
authors.initials: V
authors.lastname: Albert
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kakehi
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D011336:Probability; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D047889:Receptors, Tumor Necrosis Factor, Type II; D020169:Caspases