title: Urotensin II receptor determines prognosis of bladder cancer regulating cell motility/invasion.
abstract: BACKGROUND
  Non Muscle Invasive Bladder Transitional Cancer (NMIBC) and Muscle Invasive Bladder Transitional Cancer (MIBC)/invasive have different gene profile and clinical course. NMIBC prognosis is not completely predictable, since the relapse rate is higher than 20%, even in the form of MIBC. The aim of this study is to evaluate if UTR expression can discriminate between NMIBC and MIBC and predict the risk of relapses in NMIBCs.
  
  
  METHODS
  We have investigated upon urotensin-II (UII) receptor (UTR) expression in vivo in 159 patients affected by NMIBC. The biological role of UTR was also investigated in vitro. UTR expression was evaluated in a tissue-micro-array, consisting of normal, NMIBC and invasive bTCC samples.
  
  
  RESULTS
  UTR discriminated between NMIBC and MIBC and showed a significant correlation between low UTR expression and shorter disease free survival in NMIBC. The superagonist UPG84 induced growth suppression at nM concentrations on 3/4 cell lines. Bladder cancer cell treatment with the antagonist urantide or the knock-down of UTR with a specific shRNA significantly blocked both the motility and invasion of bladder cancer cells.
  
  
  CONCLUSIONS
  The evaluation of UTR expression can discriminate between NMIBC at high and low risk of relapse. Moreover, our data suggest that UTR is involved in the regulation of motility, invasion and proliferation of bladder cancer cells. High UTR expression is an independent prognostic factor of good prognosis for NMIBC regulating motility and invasion of bladder cancer cells.
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.forename: Silvia
authors.initials: S
authors.lastname: Zappavigna
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Gigantino
authors.forename: Amalia
authors.initials: A
authors.lastname: Luce
authors.forename: Monica
authors.initials: M
authors.lastname: Cantile
authors.forename: Margherita
authors.initials: M
authors.lastname: Cerrone
authors.forename: Gaetano
authors.initials: G
authors.lastname: Facchini
authors.forename: Sisto
authors.initials: S
authors.lastname: Perdonà
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Lorenzo
authors.forename: Sergio
authors.initials: S
authors.lastname: Chieffi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vitale
authors.forename: Marco
authors.initials: M
authors.lastname: De Sio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sgambato
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Ali Munaim
authors.initials: AM
authors.lastname: Yousif
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy. michele.caraglia@unina2.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D011379:Prognosis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014579:Urotensins / Q000494:pharmacology / Q000502:physiology
chemical_list: D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C492079:urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-; C029677:urotensin II