Enhanced expression of basement-membrane-type heparan sulfate proteoglycanin tumor fibro-myxoid stroma of intrahepatic cholangiocarcinoma

To investigate the molecular mechanism for enhanced fibrous stroma formatio n in intrahepatic cholangiocarcinoma (ICC), we surveyed the expression patt ern of basement-membrane-type heparan sulfate proteoglycan (HSPG; also know n as perlecan) at the core protein and the mRNA level in ICC as well as in other liver neoplasms and reactive hepatic diseases. Immunohistochemistry o f paraffin-embedded liver sections with hyaluronidase pretreatment showed t hat HSPG was present in small amounts in normal liver around the bile ducts and the blood vessels within the portal area. There was no evident express ion within the hepatic lobules, Intense immunoexpression of HSPG was seen i n the tumor-specific fibro-myxoid stroma of ICC and metastatic liver cancer originating from the colon. However, tumor-specific stroma of hepatocellul ar carcinomas showed little or no expression of HSPG, At the mRNA level, si gnals for HSPG were found in tumor cells of cholangiocarcinoma and metastat ic colonic carcinomas, and in myofibroblasts in the tumor fibro-myxoid-spec ific stroma, From immunoprecipitation and reverse transcription-polymerase chain reaction (RT-PCR) analyses, a cultured human intrahepatic cholangioca rcinoma cell line (CCKS1), was found to express high levels of HSPG core pr otein and mRNA, These findings suggest that biliary and metastatic colon ca rcinoma cells as well as stromal myofibroblasts have a potential for HSPG p roduction. In order to investigate the growth, invasion and metastatic abil ity of ICC, further study of the 'self-made' stromal component of ICC may p rovide a new approach.