2007 Fiscal Year Final Research Report Summary
Role of laminin alpha5 and its receptors in fibrotic liver and hepatocellular carcinoma
| Project/Area Number |
17590307
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
KIKKAWA Yamato Tokyo University of Pharmacy and Life Science, School of Pharmacy, Lecturer (20274227)
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| Co-Investigator(Kenkyū-buntansha) |
MITAKA Toshihiro Sapporo Medical University School of Medicine, Department of Pathophysiology, Professor (50231618)
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| Project Period (FY) |
2005 – 2007
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| Keywords | extarcellular matrix / laminin / integrin / lutheran / hepatocellular carcinoma / fibrotic liver / liver |
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| Research Abstract |
Laminins are a diverse group of alpha/beta/gamma heterotrimers formed from five alpha, three beta and three gamma chains ; they are major components of all basal laminae (BLs). One laminin chain that has garnered particular interest due to its widespread expression pattern and importance during development is laminin alpha5. Little is known, however, about the expression and function of laminins containing the alpha5 chain in human hepatocellular carcinoma (HCC). Here, using a specific antibody, we examined the expression of laminin alpha5 in normal liver and in HCCs. In normal liver, although laminin alpha5 was observed in hepatic BLs underlying blood vessels and bile ducts, it was absent from the parenchyma, which may be the origin of HCC. On the other hand, laminin alpha5 deposition was observed throughout all HCCs tested, regardless of tumor grade. In well differentiated HCCs, it localized along the trabecules of the tumor. In poorly-differentiated HCCs, it was present in surrounding tumor nodules. In HCC cell lines, laminin alpha5 heterotrimerized with beta and gamma chains and was secreted into the culture media. To attempt to understand the function of laminins containing alpha5, the expression of its receptors in HCCs was also determined. In this regard, alpha3betal/alpha6betal integrins and Lutheran/basal cell adhesion molecule (Lu/B-CAM) were expressed in HCC cells. In vitro studies showed that HCC cells readily attached to laminin containing the alpha5 chain, more so than did primary hepatocytes. In addition to alpha3betal/alpha6betal integrins and Lu/B-CAM, laminin alpha5 was recognized by integrin alphalbetal, which also was expressed in HCC cells. These results suggest that laminins containing alpha5 serve as functional substrates regulating progression of HCC.
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Research Products
(46 results)
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[Journal Article] Blood vessels of human islets of Langerhans are surrounded by a double basement membrane2008
Author(s)
Virtanen, I., Banerjee, M., Palgi, J., Korsgren, O., Lukinius, A., Thornell, L. E., Kikkawa, Y., Sekiguchi, K., Hukkanen, M., Konttinen, Y. T., Otonkoski, T
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Laminin alpha5 mediates ectopic adhesion of hepatocellular carcinoma through integrins and/or Lutheran/basal cell adhesion molecule2008
Author(s)
Kikkawa, Y., Sudo, R., Kon, J., Mizuguchi, T., Nomizu, M., Hirata, K., Mitaka, T
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Lutheran blood group antigen as a receptor for alpha5 laminins in gingival epithelia2007
Author(s)
Willberg, J., Hormia, M., Takkunen, M., Kikkawa. Y., Sekiguchi, K., Virtanen, I
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Journal Title
J. Periodontol 78
Pages: 1810-1818
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Integrin-dependent cell behavior on ECM peptide-conjugated chitosan membranes2007
Author(s)
Mochizuki, M., Yamagata, N., Philp, D., Hozumi, K., Watanabe, T., Kikkawa. Y., Kadoya, Y., Kleinman, H. K., Nomizu, M
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Journal Title
Biopolymers 88
Pages: 122-130
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The LG1-3 tandem of laminin alpha5 harbors the binding sites of Lutheran/basal cell adhesion molecule and alpha3beta1/alpha6beta1 integrins J. Biol. Chem2007
Author(s)
Kikkawa. Y., Sasaki, T., Nguyen, M. T., Nomizu, M., Mitaka, T., and Miner, J. H
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Journal Title
J. Biol. Chem 282
Pages: 14853-14860
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cyclic peptide analysis of the biologically active loop region in the laminin alpha3 chain LG4 module demonstrates the importance of peptide conformation on biological activity2007
Author(s)
Kato-Takagaki, K., Suzuki, N., Yokoyama, F., Takaki, S., Umezawa, K., Higo, J., Mochizuki, M., Kikkawa. Y., Oishi, S., Utani, A., Nomizu, M
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Journal Title
Biochemistry 46
Pages: 1952-1960
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Laminin-10 and Lutheran blood group glycoproteins in adhesion of human endothelial cells2006
Author(s)
Vainionpaa, N., Kikkawa, Y., Lounatmaa, K., Miner, J. H., Rousselle, P., and Virtanen, I
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Journal Title
Am. J. Physiol. Cell Physiol 290
Pages: 764-775
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Liver repopulation and long-term function of rat small hepatocyte transplantation as an alternative cell source for hepatocyte transplantation2006
Author(s)
Shibata, C., Mizuguchi, T., Kikkawa. Y., Nobuoka, T., Oshima, H., Kawasaki, H., Kawamoto, M., Katsuramaki, T., Mitaka, T., Hirata, K
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Journal Title
Liver Transpl 12
Pages: 78-87
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The immortalized human corneal epithelial cells adhere to laminin-10 by using Lutheran glycoproteins and integrin alpha3beta12005
Author(s)
Hasenson, S., Maatta, M., Rousselle, P., Kikkawa. Y., Miner, J. H., Tervo, T., Virtanen, I
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Journal Title
Exp. Eye Res 81
Pages: 415-421
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hyperbaric oxygen stimulates cell proliferation and normalizes multidrug resistance protein-2 protein localization in primary rat hepatocytes2005
Author(s)
Mizuguchi, T., Oshima, H., Imaizumi, H., Kohara, H., Kawamoto, M., Nobuoka, T., Kawasaki, H., Harada, K, Masuda, Y., Kikkawa, Y. Mitaka, T., Asai, Y., Hirata, K
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Journal Title
Wound Repair Regen 13
Pages: 551-557
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The LG1-3 tandem of laminin alpha5 harbors the binding sites of Lutheran/basal cell adhesion molecule and alpha3beta1/alpha6beta1 integrins2007
Author(s)
Kikkawa, Y., Sasaki, T., Nguyen, M.T., Nomizu, M., Mitaka, Miner, J.H
Organizer
13rd International Symposium on Basement Membranes
Place of Presentation
Cologne, Germany
Year and Date
20070900
Description
「研究成果報告書概要(欧文)」より
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