Unique epithelial cell production of hepatocyte growth factor/scatter factor by putative precancerous intestinal metaplasias and associated "intestinal-type" biliary cancer chemically induced in rat liver

Recently we observed that Met, the receptor for hepatocyte growth factor/sc atter factor (HGF/SF), is overexpressed in epithelial cells of both early-a ppearing intestinal metaplastic glands in precancerous hepatic cholangiofib rotic tissue and neoplastic glands in later developed intestinal-type of ch olangiocarcinoma originated from the furan rat model of cholangiocarcinogen esis when compared with normal and hyperplastic intrahepatic biliary epithe lia, We now show that HGF/SF is also aberrantly expressed in a manner close ly paralleling that of its receptor in the neoplastic epithelial cells of f uran-induced rat cholangiocarcinomas and in a majority of metaplastic epith elial cells within earlier formed precancerous hepatic cholangiofibrotic ti ssue. Using in situ hybridization and reverse transcription-polymerase chai n reaction (RT-PCR), we further showed specific expression of HGF/SF messen ger RNA (mRNA) in a novel rat cholangiocarcinoma epithelial cell line overe xpressing Met. This cholangiocarcinoma cell line, termed C611B, was establi shed from tumorigenic cells isolated from a furan-induced transplantable tu mor. Moreover, we detected by in situ hybridization strong expression of HG F/SF mRNA transcripts in the cancerous epithelial glands of cholangiocarcin oma 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 epithel ium. Our results clearly show that HGF/SF becomes aberrantly expressed in c holangiocarcinoma epithelium and in putative precancerous intestinal metapl astic epithelium induced in the liver of furan-treated rats.