1999 Fiscal Year Final Research Report Summary
Structural and Functional Analysis of New Type Extracellular Matrix Receptor syndecan-2
| Project/Area Number |
10680591
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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 |
Structural biochemistry
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| Research Institution | Kyoto Sangyo University |
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Principal Investigator |
OKAYAMA Minoru Kyoto Sangyo University, Professor, 工学部, 教授 (90158816)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Keiichi Mizutani Foundation for Glylycoscience, Duputy Exective Secretary, 事務局長代理
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| Project Period (FY) |
1998 – 1999
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| Keywords | Lewis lung carcinoma / extracellular matrix / fibronectin / integrin α5β1 / syndecan-2 / heparan sulfate / actin cytoskeleton / stress fiber |
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| Research Abstract |
Mouse Lewis lung carcinoma-derived low metastatic P29 clone exhibits tumorigenesis dependent on the fibronectin-rich stromal matrix, whereas the growth of highly metastatic LM66-H11 clone depends on the basement membranes. On adhesion to the fibronectin substratum in vitro, P29 cells show stress fiber formation, whereas LM66-H11 cells form cortex action structure. The phenotype of P29 cells is closely correlated to the expression of integrin α5β1 and syndrecan-2 having heparan sulfate side chains with specific affinity to COOH-terminal heparin-binding domain. LM66-H11 cells express the integrin at the same level to that of P29 cells, but syndecan-2 at a significantly lower level. On treatment of P29 cells in vitro with antisense oligonucleotide for syndecan-2, causing selective inhibition of its biosynthesis, the cells turn out to be indistinguishable from LM66-H11 cells as regards the phenotype. The phenotype of P29 cells is reproduced by adhesion to fibronectin recombinant fusion polypeptide (CH-271) comprising RGD cell-binding (C-274) and C-terminal heparin-binding (H271) comprising RGD cell-binding (C-274) and C-terminal heparin-binding (H271) domains whereas the phenotype of LM66-H11 cells in induced only by C-274 polypeptide, indicating that signaling through integrin α5β1 and syndecan-2 is essential for the polypeptide can be replaced by a large amount of H-271 polypeptide, or antibodies specific to syndecan-2 or heparan sulfate. Furthermore, when inoculated on a fusion polypeptide comprising C-274 polypeptide and basic FGF with strong affinity to syndecan-2 ectodomain, even LM66-H11 cells form stress fibers. These findings indicate the necessity of clustering of the two receptors for signaling for the organization of the actin cytoskeletons.
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[Publications] Krupinski,K., BielawuecmN,m Yoshida,K., Kyogashima,M., Takada,Y., and Takada,A.: "Dermatan sulfate enhances the lysis of laser-induced thrombus in vivo"Thrombosis Research. 91. 199-202 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamada,S., Yamane,Y., Tsuda,H., Yoshida,K., and Sugahara,K.: "A major common trisulfated hexasaccharide core sequence, hexuronic acid(2-sulfate)-glucosamine(N-sulfate)-iduronic acid-N-acetylglucosamine-glucuronic acid-glucosamine(N-sulfate), isolated from the low sulfated irregular region of porcine intestinal heparin."Journal of Biological Chemistry. 273. 1863-1871 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Liu,J., Shriver,Z., Blaiklock,P., Yoshida,K., Sasickharan,R., and Rosenberg,R.D.: "Heparan sulfate D-glucosaminyl3-0-sulfotransferase-3A sulfate N-unsubstituted glucosamine residues."Journal of Biological Chemistry. 274. 38155-38162 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Habuchi,H., Tanaka,M., Habuchi,O., Yoshida,K., Suzuki,H., Ban,K., and Kimata,K.: "The occurrence of three isoforms of heparan sulfate 6-0-sulfotransferase having different specificities for hexuronic acid adjacent to the targeted N-sulfoglucosamine."Journal of Biological Chemistry. 275. 2859-2868 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Kusano,Y., Oguri,K., Nagayasu,Y., Munesue,S., Ishihara,M.,Saiki,I., Yonekura,H., Yamamoto,H., and Okayama,M.: "Participation of syndecan 2 in the induction of stress fiber formation in cooperation with integrin α5β1 : Structural characteristics of heparin sulphate chains with avidity to COOH-terminal heparin-binding domain of fibronectin."Experimental Cell Research. (In press). (2000)
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「研究成果報告書概要(欧文)」より
