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Heparan sulfate proteoglycan on leukemic cells is primarily involved in integrin-triggering and its mediated adhesion to endothelial cells.

Research Project

Project/Area Number 07670550
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionUniversity of Occupational & Environmental Health (U.O.E.H.)

Principal Investigator

TANAKA Yoshiya  University of Occupational & Environmental Health, Medicine, Assist. Prof., 医学部, 助手 (30248562)

Co-Investigator(Kenkyū-buntansha) ETO Sumiya  University of Occupational & Environmental Health, Medicine, Professor, 医学部, 教授 (90010347)
ODA Susumu  University of Occupational & Environmental Health, Medicine, Professor, 医学部, 助教授 (80035237)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsLeukemia / Chemokine / Proteoglycan / Integrin / Adhesion / Endothelium / Metastasis
Research Abstract

Leukocyte migration from ciculation into tissue depends on leukocyte integrin-mediated adhesion to endothelium, but integrins cannot function until activated. However, it remains to be understood how tumor cells adhere to endothelium and infiltrate into underlying tissue. We studied mechanisms of extravasation of leukemic cells using adult T cell leukemia (ALT) cells and report the following novel features of cell surface heparan sulfate proteoglycan on ATL cells in ATL cell adhesion to endothelium. (1) ATL cells adhere to endothelial cells through already activated integrins without exogenous stimulation. (2) Different from any other hematopoietic cells, ATL cells express a characteristic heparan sulfate capable of immobilizing heparin-binding chemokine macrophage inflammatory protein (MIP) -1beta, a potent T cell-integrin-trigger, produced by the cells themselves. (3) Competitive interruption of endogenous heparan sulfate proteoglycan-synthesis reduces cell surface MIP-1beta and prev … More ents ATL cells from integrin-mediated adhesion to endothelial cells of ICAM-1 triggered through G-protein. (4) The heparan sulfate proteoglycan on ATL cells characteristically consists of an 100 kDa unknown core protein and extremely weakly sulfated glycosaminoglycan, which has a potency to bind to distinctive heparin-binding cytokines.
Thus, we here propose that leukemic cells adhere to endothelial cells through the adhesion cascade, similar to normal leukocyte, and that the cell surface heparan sulfate particularly on ATL cells is pivotally involved in chemokine-dependent autocrine stimulation of integrin-triggering by immobilizing the chemokine on them. This is the first study to explore the significance of interaction among heparan sulfate proteoglycan and heparin-binding cytokine for circulating tumor adhesion. Our finding would warrant further studies that different proteoglycan and cytokine might bring enormous flexibility to the process of leukemic cell infiltration and tumor metastasis and would introduce new pharmacological approaches to control them. Less

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Wake,A.: "Calcium-dependent homotypic adhesion through leukocyte function-associated antigen-1/intercellular adhesion molecule-1 induces interleukin-1 and parathyroid hormone-related protein production on adult T-cell leukemia cells in vitro." Blood. 86巻. 2257-2267 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka,Y.: "Osteoblasts are regulated by the cellular adhesion through ICAM-1 and VCAM-1." J.Bone Miner.Res.10巻. 1462-1469 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka,Y.: "Heparan sulfate proteoglycan on leukemic cells is primarily involved in integrin-triggering and its mediated adhesion to endothelial cells" J.Exp.Med.184巻. 1987-1997 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Koyama,Y.: "Cross-linking of intercellular adhesion molecule 1 (CD54) induces AP-1 activation and IL-1 β transcription" J.Immunology. 157巻11号. 5097-5103 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Abe,M.: "Regulation of interleukin (IL)-1 β gene transcription induced by IL-1 β in rheumatoid synovial fibroblast-like cells,E11,transformed with simian virus 40 large T antigen" J.Rheumatology. 24(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakatsuka,K.: "Rheumatoid Synovial Fibroblasts Are Stimulated by the Cellular Adhesion to T Cells through Lymphocyte Function Associated Antigen-1/Intercellular Adhesion Molecule-1" J.Rheumatology. 24(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka,Y.: "An Approach to diseases-Immunology,Hematology,Cancer" Adhesion molecules in inflammation., 8 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka, Y., Kimata, K., Wake, A., Mine, S., Morimoto, I., Yamakawa, N., Habuchi, H., Ashikari, S., Yamamoto, H., Sakurai, K., Yoshida, K., Suzuki, S., Eto, S.: "Heparan sulfate proteoglycan on leukemic cells is primarily involved in integrin-triggering and its mediated adhesion to endothelial cells" J.Exp. Med.184. 1987-1997 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Wake, A., Tanaka, Y., Nakatsuka, K., Misago, M., Oda, S., Morimoto, I., Eto, S.: "Calciumdependent homotypic adhesion through leukocyte function-associated antigen01/intercellular adhesion molecule-1 induces interleukin-1 and parathyroid hormone-related protein production on adult T-cell leukemia cells in vitro" Blood. 86. 2257-2267 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka, Y., Adams, D.H., & Shaw, S.: "Proteoglycans on endothelial cells present adhesioninducing cytokines to leukocytes." Immunol. Today. 14. 111-115 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka, Y., Adams, D.H., Hubscher, S., Hirano, H., Siebenlist, U., & Shaw, S.: "T-cell adhesion induced by proteoglycan-immobilized cytokine MIP-1beta." Nature. 361. 79-82 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Adams, D.A., Harvath, L., Bottaro, D.P., Interrante, R., Catalano, G., Tanaka, Y., Strain, A., Hubscher, S.G., & Shaw, S.: "Hepatocyte growth factor and macrophage inflammatory protein 1beta : structurally distinct cytokines that induce rapid cytoskeletal changes and subset-preferential migration of T cells." Proc. Natl. Acad. Sci, USA. 91. 7144-7148 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanka, Y., Morimoto, I., Nakano, Y., Okada, Y., Hirota, S., Nomura, S., Nakamura, T., Eto, S: "Osteoblasts are regulated by the cellular adhesion through ICAM-1 and VCAM-1." J.Bone Miner. Res.10. 1462-1469 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Koyama, Y., Tanaka, Y., Saito, K., Abe, M., Nakatsuka, K., Morimoto, I., Auron, P.E., Eto, S.: "Cross-linking of intercellular adhesion molecule-1 (CD54) induces AP-1 activation and interleukin-1beta transcription." J.Immunol.157. 5097-5103 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka, Y., Koyama, Y., Saito, K., Abe, M., Nakatsuka, K., Fujii, K., Adachi, T., Eto, S.: "Adhesion molecules in inflammation. In An approaches to disease : immunology, hematology, caner." Niho, Y., editor. Kyushu University Press, Fukuoka, Japan.27-34 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka, Y., Wake, A., Horgan, K.J., Murakami, S., Aso, M., Saito, K., Oda., S., Morimoto, I., Uno, H., Kikuchi, H., Izumi, Y., Eto, S.: "Distinctive phenotype of leukemic T cells with various tissue tropism." J.Immunol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka, Y., Adams, D.H., & Shaw, S.: Regulation of leukocyte recruitment by proadhesive cytokines immobilized on endothelial proteoglycan. In Adhesion in leukocyte homing and differentiation. Dunon. D., Mackay, C.R., & Imhof, B.A., editors. Springer-Verlag, Berlin, 99-108 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka, Y., M.Aso, Y.Takada.: CD29 Workshop Panel report. In Leukocyte Typing VI (ed. by Kishimoto, T., et al.). Garland Publising, New York (in press).,

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka, Y., K.Saito.: CD49d Workshop Panel report. In Leukocyte Typing VI (ed. by Kishimoto, T., et al.). Garland Publising, New York (in press).,

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Wake,A.: "Calcium-dependent homotypic adhesion through leukocyte function-associated antigen-1/intercellular adhesion molecule-1 induces interleukin-1 and parthyroid hormone-related protein production on adult T-cell leukemia cells in vitro." Blood. 86巻. 2257-2267 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Koyama,Y.: "Cross-linking of intercellular adhesion molecule 1 (CD54) induced AP-1 activation and IL-1β transcription" J.Immunology. 157巻11号. 5097-5103 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka,Y.: "Heparan sulfate proteoglycan on leukemic cells is primarily involved in integrin-triggering and its mediated adhesion to endothelial cells." J.Exp.Med.184巻. 1987-1997 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 田中良哉: "サイトカインとプロテオグリカン" アレルギー科. 2. 166-172 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 田中良哉: "サイトカインと接着分子" 臨床病理. 102. 69-77 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka,Y.: "Distinctive phenotype of leukemic T cells with various tissue tropism." J.Immunol.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] 田中良哉: "北村諭編,接着分子の基礎と臨床:最近のトピックス(医歯薬出版)" Tリンパ球の機能発現と接着分子:サイトカインとの接点, 5 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka,Y.: "Garland Publising, New York" CD29 Workshop Panel report. In Leukocyte Typing VI, in press

    • Related Report
      1996 Annual Research Report
  • [Publications] Wake, A: "Calcium-dependent homotypic adhesion through leukocyte function-associated antigen-1/intercellularadhesion molecule-1 induces interleukin-1 and parathyroid hormone-related protein production on adult T-cell leukemia cells in vitro" Blood. 86. 2257-2267 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 田中良哉: "Tリンパ球の機能発現と接着分子:サイトカインとの接点" 医学のあゆみ. 174. 13-17 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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