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

26 Citations (Scopus)

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 2006

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Cholangiocarcinoma
Biliary Tract
Hepatocytes
Hepatocellular Carcinoma
Liver
Secretin
Autoradiography
Messenger RNA
Neoplasms
Polymerase Chain Reaction
secretin receptor
Liver Neoplasms
Bicarbonates
Bile Ducts
Liver Cirrhosis
Differential Diagnosis
Up-Regulation
Hormones
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Secretin receptors in the human liver : Expression in biliary tract and cholangiocarcinoma, but not in hepatocytes or hepatocellular carcinoma. / Körner, Meike; Hayes, Gregory M.; Rehmann, Ruth; Zimmermann, Arthur; Scholz, Arne; Wiedenmann, Bertram; Miller, Laurence J; Reubi, Jean Claude.

In: Journal of Hepatology, Vol. 45, No. 6, 12.2006, p. 825-835.

Research output: Contribution to journalArticle

Körner, Meike ; Hayes, Gregory M. ; Rehmann, Ruth ; Zimmermann, Arthur ; Scholz, Arne ; Wiedenmann, Bertram ; Miller, Laurence J ; Reubi, Jean Claude. / Secretin receptors in the human liver : Expression in biliary tract and cholangiocarcinoma, but not in hepatocytes or hepatocellular carcinoma. In: Journal of Hepatology. 2006 ; Vol. 45, No. 6. pp. 825-835.
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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.",
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AU - Körner, Meike

AU - Hayes, Gregory M.

AU - Rehmann, Ruth

AU - Zimmermann, Arthur

AU - Scholz, Arne

AU - Wiedenmann, Bertram

AU - Miller, Laurence J

AU - Reubi, Jean Claude

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N2 - 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.

AB - 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.

KW - Cholangiocellular carcinoma

KW - Hepatocellular carcinoma

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KW - Receptor autoradiography

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