Urotensin II receptor determines prognosis of bladder cancer regulating cell motility/invasion

Renato Franco, Silvia Zappavigna, Vincenzo Gigantino, Amalia Luce, Monica Cantile, Margherita Cerrone, Gaetano Facchini, Sisto Perdonà, Sandro Pignata, Giuseppe Di Lorenzo, Sergio Chieffi, Giovanni Vitale, Marco De Sio, Alessandro Sgambato, Gerardo Botti, Ali Munaim Yousif, Ettore Novellino, Paolo Grieco, Michele Caraglia

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number48
JournalJournal of Experimental and Clinical Cancer Research
Volume33
Issue number1
DOIs
Publication statusPublished - Jun 3 2014

Keywords

  • Bladder cancer
  • Muscle invasive
  • Non-muscle invasive
  • Tumor progression
  • Urotensin-II

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Franco, R., Zappavigna, S., Gigantino, V., Luce, A., Cantile, M., Cerrone, M., Facchini, G., Perdonà, S., Pignata, S., Di Lorenzo, G., Chieffi, S., Vitale, G., De Sio, M., Sgambato, A., Botti, G., Yousif, A. M., Novellino, E., Grieco, P., & Caraglia, M. (2014). Urotensin II receptor determines prognosis of bladder cancer regulating cell motility/invasion. Journal of Experimental and Clinical Cancer Research, 33(1), [48]. https://doi.org/10.1186/1756-9966-33-48