Szabó Erzsébet, Korpos Eva, Batmunkh Enkhjargal, Lotz Gábor, Holczbauer Agnes, Kovalszky Ilona, Deák Ferenc, Kiss Ibolya, Schaff Zsuzsa, Kiss András
2nd Department of Pathology, Semmelweis University, Ulloi út 93, H-1091 Budapest, Hungary.
Pathol Oncol Res. 2008 Mar;14(1):15-22. doi: 10.1007/s12253-008-9005-4. Epub 2008 Apr 2.
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.
最近描述的基质连接蛋白家族是细胞外基质的一部分，然而，它们在病理生理学中的作用以及在肝脏疾病中的分布尚未得到研究。鉴于已发现基质连接蛋白在细胞生长和组织重塑中发挥作用，因此有人提出它们可能参与致癌过程。本研究的主要目的是调查作为基底膜主要成分之一的基质连接蛋白-2表达的变化。本研究使用了35例手术切除的肝细胞癌、35例相应的周围肝组织和10例正常肝样本。在35例病例中的15例中，肿瘤是在肝硬化的基础上发生的。通过免疫组织化学检测，基质连接蛋白-2蛋白表达在正常肝脏的胆管、门静脉血管周围被检测到，而肝血窦呈阴性。肝硬化周围组织在肝血窦周围显示出强烈的基质连接蛋白-2染色。免疫组织化学发现肿瘤新生血管呈强阳性。然而，基于肝细胞癌的分级，在蛋白质表达量的形态计量学方面未检测到差异。实时逆转录-聚合酶链反应未显示正常、肝硬化和肿瘤样本之间基质连接蛋白-2信使核糖核酸表达有显著差异。这表明基质连接蛋白-2的翻译后修饰表现为肝纤维化中分布的改变。我们的数据表明，基质连接蛋白-2是肝脏中一种新的基底膜成分，它在肝硬化和肝细胞癌的肝血窦“毛细血管化”过程中合成。这是第一份描述基质连接蛋白-2在人类正常肝脏、肝硬化肝脏以及肝细胞癌中的表达和分布的报告。
