Project/Area Number |
14370305
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Hematology
|
Research Institution | Yamaguchi University |
Principal Investigator |
KAWANO Michio Yamaguchi University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (40161343)
|
Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Hideaki Yamaguchi University, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (40294623)
OBATA Masanori Yamaguchi University, School of Medicine, Assistant Profssor, 医学部, 講師 (80158831)
TSUYAMA Naohiro Yamaguchi University, Graduate School of Medicine, Research Associate, 大学院・医学研究科, 助手 (10335747)
|
Project Period (FY) |
2002 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥5,200,000 (Direct Cost: ¥5,200,000)
|
Keywords | myeloma / IL-6 / CD45 / lipid rafts / immature myeloma cells / CD45 isoform / フォスファターゼ / 骨髄腫細胞 / CD19 / ラフト / 細胞膜分子動態 |
Research Abstract |
In multiple myeloma, there are quite diffrences in the surface expression of membrane proteins compared with those of normal plasma cells. Especially, a restricted number of myeloma cells express CD45 molecules and CD45RO, while normal plasma cells express CD45 and CD45RA. In addition, myeloma cells that can respond to IL-6 to proliferate are CD45-positive (CD45+) immature Myeloma cells, while CD45-negative(CD45-) Myeloma cells cannot respond to IL-6 to proliferate. In this study, we tried to clarify the role of CD45 molecules on IL-6-induced proliferation in human Myeloma cells, especially to examine the differences in their movement of CD45 isoforms after IL-6 stimulation. From this study, we found that CD45 molecules located outside lipid rafts without IL-6 stimulation, but after IL-6 stimulation CD45RO but not CD45RA moved to lipid rafts rapidly. Furthermore, we confirmed that CD45RO molecule moving to lipid rafts functioned as activator of Lyn by dephosphorylation of Tyr507 of Lyn. These results could explain why CD45+ myeloma cells(CD45RO+) but not normal plasma cells(CD45RA+) can respond to IL-6 to proliferate. In future, these results also contribute to the progress in the molecular target therapy in human myeloma.
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