Urotensin-II receptor is over-expressed in colon cancer cell lines and in colon carcinoma in humans

Alessandro Federico, Silvia Zappavigna, Marco Romano, Paolo Grieco, Amalia Luce, Monica Marra, Antonietta Gerarda Gravina, Paola Stiuso, Francesco Paolo D'Armiento, Giovanni Vitale, Concetta Tuccillo, Ettore Novellino, Carmela Loguercio, Michele Caraglia

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Urotensin (U)-II receptor (UTR) has been previously reported to be over-expressed in a number of tumours. Whether UTR-related pathway plays a role in colon carcinogenesis is unknown. Methods: We evaluated UTR protein and mRNA expression in human epithelial colon cancer cell lines and in normal colon tissue, adenomatous polyps and colon cancer. U-II protein expression was assessed in cancer cell lines. Moreover, we evaluated the effects of U-II(4-11) (an UTR agonist), antagonists and knockdown of UTR protein expression through a specific shRNA, on proliferation, invasion and motility of human colon cancer cells. Results: Cancer cell lines expressed U-II protein and UTR protein and mRNA. By immunohistochemistry, UTR was expressed in 5-30% of epithelial cells in 45 normal controls, in 30-48% in 21 adenomatous polyps and in 65-90% in 48 colon adenocarcinomas. UTR mRNA expression was increased by threefold in adenomatous polyps and eightfold in colon cancer, compared with normal colon. U-II(4-11) induced a 20-40% increase in cell growth while the blockade of the receptor with specific antagonists caused growth inhibition of 20-40%. Moreover, the knock down of UTR with a shRNA or the inhibition of UTR with the antagonist urantide induced an approximately 50% inhibition of both motility and invasion. Conclusions: UTR appears to be involved in the regulation of colon cancer cell invasion and motility. These data suggest that UTR-related pathway may play a role in colon carcinogenesis and that UTR may function as a target for therapeutic intervention in colon cancer.

Original languageEnglish
Pages (from-to)285-294
Number of pages10
JournalEuropean Journal of Clinical Investigation
Volume44
Issue number3
DOIs
Publication statusPublished - Mar 2014

Keywords

  • Colon cancer
  • Urotensin-II
  • Urotensin-II receptor

ASJC Scopus subject areas

  • Medicine(all)
  • Clinical Biochemistry
  • Biochemistry

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