Urotensin II receptor predicts the clinical outcome of prostate cancer patients and is involved in the regulation of motility of prostate adenocarcinoma cells

Paolo Grieco, Renato Franco, Giuseppina Bozzuto, Laura Toccacieli, Alessandro Sgambato, Monica Marra, Silvia Zappavigna, Mario Migaldi, Giulio Rossi, Stefano Striano, Luigi Marra, Luigi Gallo, Achille Cittadini, Gerardo Botti, Ettore Novellino, Agnese Molinari, Alfredo Budillon, Michele Caraglia

Research output: Contribution to journalArticlepeer-review

Abstract

Urotensin II (UT-II) is a potent vasoconstrictor peptide and its receptor (UTR) was correlated with human cortico-Adrenal carcinoma proliferation. In this study, we have evaluated the correlation between UTR expression and prognosis of human prostate adenocarcinoma and the involvement of this receptor in the regulation of biological properties on both in vivo and in vitro models. UTR mRNA and protein, evaluated by real-time PCR and Western blotting, respectively, were expressed at high levels only in androgen-dependent LNCaP cells. In order to investigate UTR changes occurring in human prostate tumorigenesis, we have also evaluated the expression of UTR in vivo in 195 human prostate tissue samples. UTR was always expressed at low intensity in hyperplastic tissues and at high intensity in well-differentiated carcinomas (Gleason 2-3). Moreover, we have evaluated the effects of an antagonist of UTR, urantide on migration and invasion of LNCaP cells. Urantide induced a dose-dependent decrease of motility and invasion of LNCaP cells whose characteristic ameboid movement seems to be advantageous for their malignancy. These effects were paralleled by down-regulating the autophosphorylation of focal adhesion kinase and the integrin surface expression on LNCaP cells. The effects on cell motility and invasion were likely due to the inhibition of RhoA activity induced by both urantide and shRNA UTR. These data suggest that UTR can be considered a prognostic marker in human prostate adenocarcinoma patients. J. Cell. Biochem. 112: 341-353, 2011.

Original languageEnglish
Pages (from-to)341-353
Number of pages13
JournalJournal of Cellular Biochemistry
Volume112
Issue number1
DOIs
Publication statusPublished - Jan 2011

Keywords

  • Prognostic marker
  • Prostate cancer
  • Urotensin II receptor

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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