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. 1999 Aug;80(11):1820–1825. doi: 10.1038/sj.bjc.6690604

Expression of membrane cofactor protein (MCP, CD46) in human liver diseases

N Kinugasa 1, T Higashi 1, K Nouso 1, H Nakatsukasa 1, Y Kobayashi 1, M Ishizaki 1, N Toshikuni 1, K Yoshida 1, S Uematsu 1, T Tsuji 1
PMCID: PMC2374269  PMID: 10468303

Abstract

Membrane cofactor protein (MCP, CD46) is one of the complement regulatory proteins, and is widely distributed in human organs and protects cells from complement-mediated cytotoxicity. We analysed the distribution and the intensities of MCP in liver diseases and evaluated the role of MCP during hepatocarcinogenesis. Western blot analysis revealed that relative densities (density of the sample/density of the standard sample) of MCP in 27 HCC, 18 liver cirrhosis, nine chronic hepatitis and 12 normal liver were 0.63 ± 0.23, 0.21 ± 0.07, 0.25 ± 0.10 and 0.11 ± 0.03 (mean ± s.d.) respectively. MCP expression in hepatocellular carcinoma (HCC) was significantly higher than that in both liver cirrhosis and chronic hepatitis (P < 0.01). The difference in the tumour sizes, the grades of differentiation and viral marker status did not affect the expression. Immunohistological analysis revealed that MCP was distributed mainly in the basolateral membrane of the hepatic cord in non-cancerous liver, along with endothelial cells and bile duct cells. In HCC, the protein was observed on the membrane in a non-polarized fashion. These data suggest that HCC cells acquire the increased MCP expression in a development of HCC and may escape from tumour-specific complement-mediated cytotoxicity. © 1999 Cancer Research Campaign

Keywords: membrane cofactor protein, hepatocellular carcinoma, liver, complement

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Selected References

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  1. Bjørge L., Hakulinen J., Wahlström T., Matre R., Meri S. Complement-regulatory proteins in ovarian malignancies. Int J Cancer. 1997 Jan 6;70(1):14–25. doi: 10.1002/(sici)1097-0215(19970106)70:1<14::aid-ijc3>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  2. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  3. Cheung N. K., Walter E. I., Smith-Mensah W. H., Ratnoff W. D., Tykocinski M. L., Medof M. E. Decay-accelerating factor protects human tumor cells from complement-mediated cytotoxicity in vitro. J Clin Invest. 1988 Apr;81(4):1122–1128. doi: 10.1172/JCI113426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Davies A., Simmons D. L., Hale G., Harrison R. A., Tighe H., Lachmann P. J., Waldmann H. CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells. J Exp Med. 1989 Sep 1;170(3):637–654. doi: 10.1084/jem.170.3.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gorter A., Blok V. T., Haasnoot W. H., Ensink N. G., Daha M. R., Fleuren G. J. Expression of CD46, CD55, and CD59 on renal tumor cell lines and their role in preventing complement-mediated tumor cell lysis. Lab Invest. 1996 Jun;74(6):1039–1049. [PubMed] [Google Scholar]
  6. Hakulinen J., Meri S. Expression and function of the complement membrane attack complex inhibitor protectin (CD59) on human breast cancer cells. Lab Invest. 1994 Dec;71(6):820–827. [PubMed] [Google Scholar]
  7. Hofman P., Hsi B. L., Manie S., Fenichel P., Thyss A., Rossi B. High expression of the antigen recognized by the monoclonal antibody GB24 on human breast carcinomas: a preventive mechanism of malignant tumor cells against complement attack? Breast Cancer Res Treat. 1994;32(2):213–219. doi: 10.1007/BF00665772. [DOI] [PubMed] [Google Scholar]
  8. Hourcade D., Holers V. M., Atkinson J. P. The regulators of complement activation (RCA) gene cluster. Adv Immunol. 1989;45:381–416. doi: 10.1016/s0065-2776(08)60697-5. [DOI] [PubMed] [Google Scholar]
  9. Inoue H., Mizuno M., Uesu T., Ueki T., Tsuji T. Distribution of complement regulatory proteins, decay-accelerating factor, CD59/homologous restriction factor 20 and membrane cofactor protein in human colorectal adenoma and cancer. Acta Med Okayama. 1994 Oct;48(5):271–277. doi: 10.18926/AMO/31112. [DOI] [PubMed] [Google Scholar]
  10. Johnstone R. W., Loveland B. E., McKenzie I. F. Identification and quantification of complement regulator CD46 on normal human tissues. Immunology. 1993 Jul;79(3):341–347. [PMC free article] [PubMed] [Google Scholar]
  11. Lachmann P. J. The control of homologous lysis. Immunol Today. 1991 Sep;12(9):312–315. doi: 10.1016/0167-5699(91)90005-E. [DOI] [PubMed] [Google Scholar]
  12. Liszewski M. K., Post T. W., Atkinson J. P. Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu Rev Immunol. 1991;9:431–455. doi: 10.1146/annurev.iy.09.040191.002243. [DOI] [PubMed] [Google Scholar]
  13. Lublin D. M., Atkinson J. P. Decay-accelerating factor: biochemistry, molecular biology, and function. Annu Rev Immunol. 1989;7:35–58. doi: 10.1146/annurev.iy.07.040189.000343. [DOI] [PubMed] [Google Scholar]
  14. Maisner A., Liszewski M. K., Atkinson J. P., Schwartz-Albiez R., Herrler G. Two different cytoplasmic tails direct isoforms of the membrane cofactor protein (CD46) to the basolateral surface of Madin-Darby canine kidney cells. J Biol Chem. 1996 Aug 2;271(31):18853–18858. doi: 10.1074/jbc.271.31.18853. [DOI] [PubMed] [Google Scholar]
  15. Matsumoto M., Seya T., Nagasawa S. Polymorphism and proteolytic fragments of granulocyte membrane cofactor protein (MCP, CD46) of complement. Biochem J. 1992 Jan 15;281(Pt 2):493–499. doi: 10.1042/bj2810493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Matsumura N., Tagami H., Hotta T., Takemura S., Yoshikawa T., Kondo M. [Serum complement profile and its clinical significance in patients with hepatocellular carcinoma and liver cirrhosis (author's transl)]. Nihon Shokakibyo Gakkai Zasshi. 1981 Sep;78(9):1753–1759. [PubMed] [Google Scholar]
  17. McNearney T., Ballard L., Seya T., Atkinson J. P. Membrane cofactor protein of complement is present on human fibroblast, epithelial, and endothelial cells. J Clin Invest. 1989 Aug;84(2):538–545. doi: 10.1172/JCI114196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mäenpä A., Junnikkala S., Hakulinen J., Timonen T., Meri S. Expression of complement membrane regulators membrane cofactor protein (CD46), decay accelerating factor (CD55), and protectin (CD59) in human malignant gliomas. Am J Pathol. 1996 Apr;148(4):1139–1152. [PMC free article] [PubMed] [Google Scholar]
  19. Nagura H., Hasegawa H., Yoshimura S., Watanabe K. The third (C3) and fourth (C4) components of complement in human liver. Immunocytochemical evidence for hepatocytes as the site of synthesis. Acta Pathol Jpn. 1985 Jan;35(1):71–78. doi: 10.1111/j.1440-1827.1985.tb02206.x. [DOI] [PubMed] [Google Scholar]
  20. Niehans G. A., Cherwitz D. L., Staley N. A., Knapp D. J., Dalmasso A. P. Human carcinomas variably express the complement inhibitory proteins CD46 (membrane cofactor protein), CD55 (decay-accelerating factor), and CD59 (protectin). Am J Pathol. 1996 Jul;149(1):129–142. [PMC free article] [PubMed] [Google Scholar]
  21. Post T. W., Liszewski M. K., Adams E. M., Tedja I., Miller E. A., Atkinson J. P. Membrane cofactor protein of the complement system: alternative splicing of serine/threonine/proline-rich exons and cytoplasmic tails produces multiple isoforms that correlate with protein phenotype. J Exp Med. 1991 Jul 1;174(1):93–102. doi: 10.1084/jem.174.1.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Scoazec J. Y., Delautier D., Moreau A., Durand F., Degott C., Benhamou J. P., Belghiti J., Feldmann G. Expression of complement-regulatory proteins in normal and UW-preserved human liver. Gastroenterology. 1994 Aug;107(2):505–516. doi: 10.1016/0016-5085(94)90178-3. [DOI] [PubMed] [Google Scholar]
  23. Seya T., Atkinson J. P. Functional properties of membrane cofactor protein of complement. Biochem J. 1989 Dec 1;264(2):581–588. doi: 10.1042/bj2640581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Seya T., Hara T., Matsumoto M., Sugita Y., Akedo H. Complement-mediated tumor cell damage induced by antibodies against membrane cofactor protein (MCP, CD46). J Exp Med. 1990 Dec 1;172(6):1673–1680. doi: 10.1084/jem.172.6.1673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Seya T., Matsumoto M., Hara T., Hatanaka M., Masaoka T., Akedo H. Distribution of C3-step regulatory proteins of the complement system, CD35 (CR1), CD46 (MCP), and CD55 (DAF), in hematological malignancies. Leuk Lymphoma. 1994 Feb;12(5-6):395–400. doi: 10.3109/10428199409073780. [DOI] [PubMed] [Google Scholar]
  26. Simpson K. L., Houlihan J. M., Holmes C. H. Complement regulatory proteins in early human fetal life: CD59, membrane co-factor protein (MCP) and decay-accelerating factor (DAF) are differentially expressed in the developing liver. Immunology. 1993 Oct;80(2):183–190. [PMC free article] [PubMed] [Google Scholar]
  27. Simpson K. L., Jones A., Norman S., Holmes C. H. Expression of the complement regulatory proteins decay accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46) and CD59 in the normal human uterine cervix and in premalignant and malignant cervical disease. Am J Pathol. 1997 Nov;151(5):1455–1467. [PMC free article] [PubMed] [Google Scholar]

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