PMID- 10827151 OWN - NLM STAT- MEDLINE DCOM- 20000621 LR - 20240513 IS - 0270-9139 (Print) IS - 0270-9139 (Linking) VI - 31 IP - 6 DP - 2000 Jun TI - 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. PG - 1257-65 AB - 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. FAU - Lai, G H AU - Lai GH AD - Department of Pathology, The Medical School at Virginia Commonwealth University, Richmond, VA 23298-0297, USA. FAU - Radaeva, S AU - Radaeva S FAU - Nakamura, T AU - Nakamura T FAU - Sirica, A E AU - Sirica AE LA - eng GR - 1R01 CA83650/CA/NCI NIH HHS/United States GR - 5R01 CA39225/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Hepatology JT - Hepatology (Baltimore, Md.) JID - 8302946 RN - 67256-21-7 (Hepatocyte Growth Factor) SB - IM MH - Animals MH - Bile Duct Neoplasms/chemically induced/*metabolism/pathology MH - *Bile Ducts, Intrahepatic MH - Blotting, Northern MH - Cholangiocarcinoma/metabolism/pathology MH - Epithelial Cells/metabolism MH - Hepatocyte Growth Factor/*biosynthesis MH - Immunohistochemistry MH - In Situ Hybridization MH - Intestinal Neoplasms/*metabolism MH - Intestines/pathology MH - Male MH - Metaplasia MH - Precancerous Conditions/*metabolism MH - Rats MH - Rats, Inbred F344 MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Cells, Cultured EDAT- 2000/05/29 09:00 MHDA- 2000/06/24 11:00 CRDT- 2000/05/29 09:00 PHST- 2000/05/29 09:00 [pubmed] PHST- 2000/06/24 11:00 [medline] PHST- 2000/05/29 09:00 [entrez] AID - S0270913900988918 [pii] AID - 10.1053/jhep.2000.8108 [doi] PST - ppublish SO - Hepatology. 2000 Jun;31(6):1257-65. doi: 10.1053/jhep.2000.8108.