Lai G H, Radaeva S, Nakamura T, Sirica A E
Department of Pathology, The Medical School at Virginia Commonwealth University, Richmond, VA 23298-0297, USA.
Hepatology. 2000 Jun;31(6):1257-65. doi: 10.1053/jhep.2000.8108.
Recently, we observed that Met, the receptor for hepatocyte growth factor/scatter factor (HGF/SF), is overexpressed in epithelial cells of both early-appearing intestinal metaplastic glands in precancerous hepatic cholangiofibrotic tissue and neoplastic glands in later developed intestinal-type of cholangiocarcinoma originated from the furan rat model of cholangiocarcinogenesis when compared with normal and hyperplastic intrahepatic biliary epithelia. We now show that HGF/SF is also aberrantly expressed in a manner closely paralleling that of its receptor in the neoplastic epithelial cells of furan-induced rat cholangiocarcinomas and in a majority of metaplastic epithelial cells within earlier formed precancerous hepatic cholangiofibrotic tissue. Using in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR), we further showed specific expression of HGF/SF messenger RNA (mRNA) in a novel rat cholangiocarcinoma epithelial cell line overexpressing Met. This cholangiocarcinoma cell line, termed C611B, was established from tumorigenic cells isolated from a furan-induced transplantable tumor. Moreover, we detected by in situ hybridization strong expression of HGF/SF mRNA transcripts in the cancerous epithelial glands of cholangiocarcinoma developed in recipient rats after in vivo cell transplantation of C611B cells. In contrast, mRNA transcripts and protein immunoreactivity for this cytokine were not detected in hepatocytes and biliary epithelial cells in adult normal rat liver nor in rat hyperplastic intrahepatic biliary epithelium. Our results clearly show that HGF/SF becomes aberrantly expressed in cholangiocarcinoma epithelium and in putative precancerous intestinal metaplastic epithelium induced in the liver of furan-treated rats.
最近，我们观察到，与正常和增生的肝内胆管上皮相比，肝细胞生长因子/离散因子（HGF/SF）的受体Met在癌前肝胆管纤维组织中早期出现的肠化生腺体的上皮细胞以及后来发生的源自胆管癌发生的呋喃大鼠模型的肠型胆管癌的肿瘤腺体中均过表达。我们现在表明，HGF/SF在呋喃诱导的大鼠胆管癌的肿瘤上皮细胞以及早期形成的癌前肝胆管纤维组织中的大多数化生上皮细胞中也以与其受体密切平行的方式异常表达。使用原位杂交和逆转录聚合酶链反应（RT-PCR），我们进一步显示了HGF/SF信使核糖核酸（mRNA）在一种过表达Met的新型大鼠胆管癌细胞系中的特异性表达。这种胆管癌细胞系称为C611B，是从从呋喃诱导的可移植肿瘤中分离出的致瘤细胞建立的。此外，我们通过原位杂交检测到，在将C611B细胞进行体内细胞移植后，受体大鼠发生的胆管癌的癌上皮腺体中HGF/SF mRNA转录物的强烈表达。相比之下，在成年正常大鼠肝脏的肝细胞和胆管上皮细胞以及大鼠增生的肝内胆管上皮中未检测到这种细胞因子的mRNA转录物和蛋白免疫反应性。我们的结果清楚地表明，HGF/SF在呋喃处理的大鼠肝脏中诱导的胆管癌上皮和假定的癌前肠化生上皮中异常表达。
