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Expression of Matrilin-2 in Liver Cirrhosis and Hepatocellular Carcinoma

  • Original Paper
  • Published:
Pathology & Oncology Research

Abstract

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.

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Abbreviations

HCC:

hepatocellular carcinoma

ECM:

extracellular matrix

References

  1. Monto A, Wright TL (2001) The epidemiology and prevention of hepatocellular carcinoma. Semin Oncol 28:441–449

    Article  PubMed  CAS  Google Scholar 

  2. Wu XZ, Chen D, Xie GR (2006) Extracellular matrix remodeling in hepatocellular carcinoma: effects of soil on seed? Med Hypotheses 66:1115–1120

    Article  PubMed  CAS  Google Scholar 

  3. 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

    Article  PubMed  CAS  Google Scholar 

  4. Assoian RK, Marcantonio EE (1997) The extracellular matrix as a cell cycle control element in atherosclerosis and restenosis. J Clin Invest 100:15–18

    Google Scholar 

  5. Ingber DE, Folkman J (1989) How does extracellular matrix control capillary morphogenesis? Cell 58:803–805

    Article  PubMed  CAS  Google Scholar 

  6. Juliano RL, Haskill S (1993) Signal transduction from the extracellular matrix. J Cell Biol 120:577–585

    Article  PubMed  CAS  Google Scholar 

  7. 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

    PubMed  CAS  Google Scholar 

  8. 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

    Article  PubMed  CAS  Google Scholar 

  9. Deak F, Wagener R, Kiss I, Paulsson M (1999) The matrilins: a novel family of oligomeric extracellular matrix proteins. Matrix Biol 18:55–64

    Article  PubMed  CAS  Google Scholar 

  10. Belluoccio D, Trueb B (1997) Matrilin-3 from chicken cartilage. FEBS Lett 415:212–216

    Article  PubMed  CAS  Google Scholar 

  11. 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

    Article  Google Scholar 

  12. Paulsson M, Heinegard D (1979) Matrix proteins bound to associatively prepared proteoglycans from bovine cartilage. Biochem J 183:539–545

    PubMed  CAS  Google Scholar 

  13. Paulsson M, Heinegard D (1981) Purification and structural characterization of a cartilage matrix protein. Biochem J 197:367–375

    PubMed  CAS  Google Scholar 

  14. 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

    Article  PubMed  CAS  Google Scholar 

  15. Klatt AR, Paulsson M, Wagener R (2002) Expression of matrilins during maturation of mouse skeletal tissues. Matrix Biol 21:289–296

    Article  PubMed  CAS  Google Scholar 

  16. 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

    Article  PubMed  CAS  Google Scholar 

  17. 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

    Article  PubMed  CAS  Google Scholar 

  18. 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

    Article  PubMed  Google Scholar 

  19. 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

    Article  PubMed  CAS  Google Scholar 

  20. 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

    Article  PubMed  CAS  Google Scholar 

  21. 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

    PubMed  CAS  Google Scholar 

  22. 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

    Article  CAS  Google 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 1:30–36

    Google Scholar 

  24. 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

    Article  PubMed  CAS  Google Scholar 

  25. Kin M, Torimura T, Ueno T, Inuzuka S, Tanikawa K (1994) Sinusoidal capillarization in small hepatocellular carcinoma. Pathology International 44:771–778

    PubMed  CAS  Google Scholar 

  26. 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

    Article  PubMed  CAS  Google Scholar 

  27. Shiojiri N, Sugiyama Y (2004) Immunolocalization of extracellular matrix components and integrins during mouse liver development. Hepatology 40:346–355

    Article  PubMed  CAS  Google Scholar 

  28. 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

    PubMed  Google 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 38:1508–1515

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

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.

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Authors and Affiliations

  1. 2nd Department of Pathology, Semmelweis University, Üllői út 93, H-1091, Budapest, Hungary

    Erzsébet Szabó, Enkhjargal Batmunkh, Gábor Lotz, Ágnes Holczbauer, Zsuzsa Schaff & András Kiss

  2. Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary

    Éva Korpos, Ferenc Deák & Ibolya Kiss

  3. 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

    Ilona Kovalszky

Authors
  1. Erzsébet Szabó
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  2. Éva Korpos
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  3. Enkhjargal Batmunkh
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  4. Gábor Lotz
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  5. Ágnes Holczbauer
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  6. Ilona Kovalszky
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  7. Ferenc Deák
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  8. Ibolya Kiss
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  9. Zsuzsa Schaff
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  10. András Kiss
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Corresponding author

Correspondence to Zsuzsa Schaff.

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Szabó, E., Korpos, É., Batmunkh, E. et al. Expression of Matrilin-2 in Liver Cirrhosis and Hepatocellular Carcinoma. Pathol. Oncol. Res. 14, 15–22 (2008). https://doi.org/10.1007/s12253-008-9005-4

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  • DOI: https://doi.org/10.1007/s12253-008-9005-4

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