Secretin receptors in the human liver:: Expression in biliary tract and cholangiocarcinoma, but not in hepatocytes or hepatocellular carcinoma
Secretin receptors in the human liver:: Expression in biliary tract and cholangiocarcinoma, but not in hepatocytes or hepatocellular carcinoma
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DOI：
10.1016/j.jhep.2006.06.016
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发表时间：
2006-12-01
影响因子：
25.7
通讯作者：
Reubi, Jean Claude
中科院分区：
文献类型：
--
作者：
Korner, Meike;Hayes, Gregory M.;Reubi, Jean Claude
背景/目的：肠道激素受体在人类癌症中过度表达，并允许受体靶向肿瘤成像和治疗。用于这些目的的一种新的有希望的受体是促胰液素受体。在人肝脏中研究促分泌素受体表达，因为肝脏是促分泌素的生理靶点，并且因为肝癌需要新的诊断和治疗方式。19个正常肝脏，10个硬化肝脏，35个胆管癌，用I-125-[Tyr（10）]进行体外受体放射自显影，研究45例肝细胞癌中促胰液素受体的表达结果：正常大鼠胆管和小胆管中存在分泌素受体，肝细胞中无分泌素受体。在肝硬化的小管反应中观察到显著的受体上调。22例（63%）胆管癌分泌素受体阳性，而肝细胞癌为阴性。RT-PCR显示非肿瘤性肝脏中存在野生型受体mRNA，放射自显影实验中胆管癌中存在野生型和剪接变体受体mRNA，放射自显影阴性胆管癌中无受体转录本。分泌素受体在胆道中的表达是分泌素诱导的重碳酸盐血症的分子基础。受体在胆管癌中的高表达可用于这些肿瘤的体内分泌素受体靶向以及用于与肝细胞癌的鉴别诊断。(c)2006年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
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 I-125-[Tyr(10)] 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. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.