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

Fingerprint

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.
@article{36344891dc7d43fdab7113373a9d8f8b,
title = "Secretin receptors in the human liver: Expression in biliary tract and cholangiocarcinoma, but not in hepatocytes or hepatocellular carcinoma",
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.",
keywords = "Cholangiocellular carcinoma, Hepatocellular carcinoma, Human liver, Receptor autoradiography, Secretin receptor",
author = "Meike K{\"o}rner and Hayes, {Gregory M.} and Ruth Rehmann and Arthur Zimmermann and Arne Scholz and Bertram Wiedenmann and Miller, {Laurence J} and Reubi, {Jean Claude}",
year = "2006",
month = "12",
doi = "10.1016/j.jhep.2006.06.016",
language = "English (US)",
volume = "45",
pages = "825--835",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier",
number = "6",

}

TY - JOUR

T1 - Secretin receptors in the human liver

T2 - Expression in biliary tract and cholangiocarcinoma, but not in hepatocytes or hepatocellular carcinoma

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

PY - 2006/12

Y1 - 2006/12

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

KW - Human liver

KW - Receptor autoradiography

KW - Secretin receptor

UR - http://www.scopus.com/inward/record.url?scp=33750442885&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750442885&partnerID=8YFLogxK

U2 - 10.1016/j.jhep.2006.06.016

DO - 10.1016/j.jhep.2006.06.016

M3 - Article

VL - 45

SP - 825

EP - 835

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 6

ER -