Expression of Matrilin-2 in Liver Cirrhosis and Hepatocellular Carcinoma
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The recently described matrilin protein family is part of the extracellular matrix, their pathophysiological role as well as distribution in liver diseases, however, have not yet been studied. Considering that matrilins have been found to play role in cell growth and tissue remodeling, their possible involvement in carcinogenesis has been raised. The main objective of this study was to investigate the changes in matrilin-2 expression which is one of the main components of basement membranes. Thirty-five cases of surgically resected hepatocellular carcinomas, 35 corresponding surrounding liver tissues and 10 normal liver samples were used for the study. In 15 of 35 cases the tumor developed on the basis of cirrhosis. Matrilin-2 protein expression was detected in normal liver around bile ducts, portal blood vessels, while sinusoids were negative by immunohistochemistry. Cirrhotic surrounding tissue showed intensive matrilin-2 staining along the sinusoids. Tumorous neovasculature was found strongly positive by immunohistochemistry. No differences, however, were detected by morphometry regarding the amount of protein expression based on the grade of hepatocellular carcinomas. Real-time RT-PCR did not show significant differences in matrilin-2 mRNA expression between normal, cirrhotic and tumor samples. This suggests posttranslational modification of matrilin-2 manifesting in altered distribution in liver fibrosis. Our data indicate that matrilin-2 is a novel basement membrane component in the liver, which is synthetised during sinusoidal “capillarization” in cirrhosis and in hepatocellular carcinoma. This is the first report to describe the expression and distribution of matrilin-2 in human normal and cirrhotic liver as well as in hepatocellular carcinoma.
KeywordsMatrilin-2 Basement membrane Extracellular matrix Hepatocellular carcinoma Cirrhosis
The authors thank Magdolna Pekár, Ágnes Szík for their skilful technical assistance.
This study was supported by the following grants: NKFP-1A /002/056/2004, ETT-049/2006, ETT-156/2006, ETT 008/2006 from the Ministry of Health and OTKA-T049559, OTKA T049608 from the Hungarian National Scientific Research Foundation.
- 4.Assoian RK, Marcantonio EE (1997) The extracellular matrix as a cell cycle control element in atherosclerosis and restenosis. J Clin Invest 100:15–18Google Scholar
- 23.Pfaffl MW, Horgan GW, Dempfle L (2002) Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 1:30–36Google Scholar
- 29.Batmunkh E, Tátrai P, Szabó E, Lódi Cs, Holczbauer Á, Páska Cs, Kupcsulik P, Kiss A, Schaff Zs, Kovalszky I (2007) Comparison of the expression of agrin, a basement membrane heparan sulfate proteoglycan, in cholangiocarcinoma and hepatocellular carcinoma. Hum Pathol 38:1508–1515PubMedCrossRefGoogle Scholar