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
N1 - Funding Information:
We would like to thank Dr Peter Neuhaus, Department of General, Visceral and Transplantation Surgery, Charité, Campus Virchow, Berlin, Germany, for the generous gift of the majority of the tumors in the present study. Grant support : The study was supported by grant DK46577 from the National Institutes of Health.
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
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U2 - 10.1016/j.jhep.2006.06.016
DO - 10.1016/j.jhep.2006.06.016
M3 - Article
C2 - 16935383
AN - SCOPUS:33750442885
SN - 0168-8278
VL - 45
SP - 825
EP - 835
JO - Journal of hepatology
JF - Journal of hepatology
IS - 6
ER -