Expression pattern of collagen XVIII in HCC

Abstract

T. Cramer. M. Bauer. l H. Herb&. E.O. Riecken. D. Schupoan. Dept. of Gastroenterology, Klinikum 6. Franklin, Free Univ. of Berlin; Institute of Pathology, ‘Klinikum Eppendorf, Univ. of Hamburg; Germany. Background: Collagen XVIII (CXVIII), a novel basement membrane collagen, is mainly expressed in liver. Notably, a 20 kDa C-terminal fragment of CXVIII is the potent angiogenesis inhibitor endostatin, possibly by blocking endothelial cell attachment to CXVIII. Using in situ hybri-dization we could show that CXVIII is mainly produced by hepatocytes. However, its expression pattern in HCC is unknown. Methods: We amplified segments of the CXVIII gene encoding endostatin and the triple helical region by PCR to generate [35S]-UTP-labeled riboprobes. In situ hybridization combined with immunohistochemistry for cell specific markers was performed on 2 normal livers and 16 samples of HCC with adjacent cirrhotic liver tissue (HBV: n=4; HCV: n=12). Results: All hepatocytes of normal and cirrhotic liver showed strong autoradiographic signals for CXVIII RNA. Weaker signals were found over bile duct epithelia, whereas scattered capillary endothelia and smooth muscle cells, but no stellate cells displayed occasional transcripts. CXVIII expression over all HCC cells was higher than in normal liver, but comparable to the enhanced levels of hepatocytes in regenerative nodules. Conclusions: 1) Contrary to all other collagens expression of CXVIII is restricted to hepatocytes and biliary epithelia. 2) Elevated transcription of the CXVIII gene by cirrhotic and neoplastic hepatocytes could fuel angiogenesis in HCC. ( P/c04/015 )