Expression of Matrilin-2 in Liver Cirrhosis and Hepatocellular Carcinoma
Tóm tắt
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.
Tài liệu tham khảo
Monto A, Wright TL (2001) The epidemiology and prevention of hepatocellular carcinoma. Semin Oncol 28:441–449
Wu XZ, Chen D, Xie GR (2006) Extracellular matrix remodeling in hepatocellular carcinoma: effects of soil on seed? Med Hypotheses 66:1115–1120
Damsky CH, Werb Z (1992) Signal transduction by integrin receptors for extracellular matrix: cooperative processing of extracellular information. Curr Opin Cell Biol 4:772–781
Assoian RK, Marcantonio EE (1997) The extracellular matrix as a cell cycle control element in atherosclerosis and restenosis. J Clin Invest 100:15–18
Ingber DE, Folkman J (1989) How does extracellular matrix control capillary morphogenesis? Cell 58:803–805
Juliano RL, Haskill S (1993) Signal transduction from the extracellular matrix. J Cell Biol 120:577–585
Droz D, Patly N, Paraf F, Chretien Y, Gogusev J (1994) Composition of extracellular matrix and distribution of cell adhesion molecules in renal cell tumors. Lab Invest 71:710–718
Deak F, Piecha D, Bachrati C, Paulsson M, Kiss I (1997) Primary structure and expression of matrilin-2, the closest relative of cartilage matrix protein within the von Willebrand factor type A-like module superfamily. J Biol Chem 272:9268–9274
Deak F, Wagener R, Kiss I, Paulsson M (1999) The matrilins: a novel family of oligomeric extracellular matrix proteins. Matrix Biol 18:55–64
Belluoccio D, Trueb B (1997) Matrilin-3 from chicken cartilage. FEBS Lett 415:212–216
Wagener R, Ehlen HW, Ko YP, Kobbe B, Mann HH, Sengle G, Paulsson M (2005) The matrilins—adaptor proteins in the extracellular matrix. FEBS Lett 79:3323–3329
Paulsson M, Heinegard D (1979) Matrix proteins bound to associatively prepared proteoglycans from bovine cartilage. Biochem J 183:539–545
Paulsson M, Heinegard D (1981) Purification and structural characterization of a cartilage matrix protein. Biochem J 197:367–375
Piecha D, Muratoglu S, Morgelin M, Hauser N, Studer D, Kiss I, Paulsson M, Deak F (1999) Matrilin-2, a large, oligomeric matrix protein, is expressed by a great variety of cells and forms fibrillar networks. J Biol Chem 274:13353–13361
Klatt AR, Paulsson M, Wagener R (2002) Expression of matrilins during maturation of mouse skeletal tissues. Matrix Biol 21:289–296
Piecha D, Hartmann K, Kobbe B, Haase I, Mauch C, Krieg T, Paulsson M (2002) Expression of matrilin-2 in human skin. J Invest Dermatol 119:38–43
Segat D, Frie C, Nitsche PD, Klatt AR, Piecha D, Korpos E, Deak F, Wagener R, Paulssson M, Smyth N (2000) Expression of matrilin-1, -2 and -3 in developing mouse limbs and heart. Matrix Biol 19:649–655
Szabó E, Lódi C, Korpos E, Batmunkh E, Rottenberger Z, Deák F, Kiss I, Tokés AM, Lotz G, László V, Kiss A, Schaff Z, Nagy P (2007) Expression of matrilin-2 in oval cells during rat liver regeneration. Matrix Biol 26:554–560
Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN (1995) Histological grading and staging of chronic hepatitis. J Hepatol 22:696–699
Korpos E, Molnar A, Papp P, Kiss I, Orosz L, Deak F (2005) Expression pattern of matrilins and other extracellular matrix proteins characterize distinct stages of cell differentiation during antler development. Matrix Biol 24:124–135
Merz H, Malisius R, Mannweiler S, Zhou R, Hartmann W, Orscheschek K, Moubayed P, Feller AC (1995) ImmunoMax. A maximized immunohistochemical method for the retrieval and enhancement of hidden antigens. Lab Invest 73:149–156
Mannhalter C, Koizar D, Mitterbauer G (2000) Evalution of RNA isolation methods and reference genes for RT-PCR analyses of rare target RNA. Clin Lab Med 38:171–177
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 1:30–36
Sharma MK, Watson MA, Lyman M, Perry A, Aldape KD, Deak F, Gutmann DH (2006) Matrilin-2 expression distinguishes clinically relevant subsets of pilocytic astrocytoma. Neurology 66:127–130
Kin M, Torimura T, Ueno T, Inuzuka S, Tanikawa K (1994) Sinusoidal capillarization in small hepatocellular carcinoma. Pathology International 44:771–778
Mates L, Korpos E, Deak F, Liu Z, Beier DR, Aszodi A, Kiss I (2002) Comparative analysis of the mouse and human genes (Matn2 and MATN2) for matrilin-2, a filament-forming protein widely distributed in extracellular matrices. Matrix Biol 21:163–174
Shiojiri N, Sugiyama Y (2004) Immunolocalization of extracellular matrix components and integrins during mouse liver development. Hepatology 40:346–355
Tátrai P, Dudás J, Batmunkh E, Mathe M, Zalatnai A, Schaff Z, Ramadori G, Kovalszky I (2006) Agrin, a novel basement membrane component in human and rat liver, accumulates in cirrhosis and hepatocellular carcinoma. Lab Invest 86:1149–1160
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 38:1508–1515