1996 Fiscal Year Final Research Report Summary
Heparan sulfate proteoglycan on leukemic cells is primarily involved in integrin-triggering and its mediated adhesion to endothelial cells.
| Project/Area Number |
07670550
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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 |
内科学一般
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| Research Institution | University of Occupational & Environmental Health (U.O.E.H.) |
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Principal Investigator |
TANAKA Yoshiya University of Occupational & Environmental Health, Medicine, Assist. Prof., 医学部, 助手 (30248562)
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| 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)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Leukemia / Chemokine / Proteoglycan / Integrin / Adhesion / Endothelium / Metastasis |
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| 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
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[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
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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).
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[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)
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