Secretin receptors in the human liver: Expression in biliary tract and cholangiocarcinoma, but not in hepatocytes or hepatocellular carcinoma

Meike Körner, Gregory M. Hayes, Ruth Rehmann, Arthur Zimmermann, Arne Scholz, Bertram Wiedenmann, Laurence J. Miller, Jean Claude Reubi

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Background/Aims: Gut hormone receptors are over-expressed in human cancer and allow receptor-targeted tumor imaging and therapy. A novel promising receptor for these purposes is the secretin receptor. The secretin receptor expression was investigated in the human liver because the liver is a physiological secretin target and because novel diagnostic and treatment modalities are needed for liver cancer. Methods: Nineteen normal livers, 10 cirrhotic livers, 35 cholangiocarcinomas, and 45 hepatocellular carcinomas were investigated for secretin receptor expression by in vitro receptor autoradiography using 125I-[Tyr10] rat secretin and, in selected cases, for secretin receptor mRNA by RT-PCR. Results: Secretin receptors were present in normal bile ducts and ductules, but not in hepatocytes. A significant receptor up-regulation was observed in ductular reaction in liver cirrhosis. Twenty-two (63%) cholangiocarcinomas were positive for secretin receptors, while hepatocellular carcinomas were negative. RT-PCR revealed wild-type receptor mRNA in the non-neoplastic liver, wild-type and spliced variant receptor mRNAs in cholangiocarcinomas found receptor positive in autoradiography experiments, and no receptor transcripts in autoradiographically negative cholangiocarcinomas. Conclusions: The expression of secretin receptors in the biliary tract is the molecular basis of the secretin-induced bicarbonate-rich choleresis in man. The high receptor expression in cholangiocarcinomas may be used for in vivo secretin receptor-targeting of these tumors and for the differential diagnosis with hepatocellular carcinoma.

Original languageEnglish (US)
Pages (from-to)825-835
Number of pages11
JournalJournal of hepatology
Volume45
Issue number6
DOIs
StatePublished - Dec 1 2006

Keywords

  • Cholangiocellular carcinoma
  • Hepatocellular carcinoma
  • Human liver
  • Receptor autoradiography
  • Secretin receptor

ASJC Scopus subject areas

  • Hepatology

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