The mechanism of translocation of CD45R0 to lipid rafts in IL-6-induced proliferation of human myeloma cells

IL-6诱导人骨髓瘤细胞增殖中CD45R0易位至脂筏的机制

• 批准号: 17591000
• 负责人: KAWANO Michio
• 金额: $ 2.24万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591000/
• 关键词: myeloma cells; CD45; CD45R0; CD45RA; lipid rafts; signal transduction; Galectin-1; IL-6; 骨髄腫; CD-45

Human myeloma cells show the different surface antigen expressions from those in norma bone marrow plasma cells; especially, all normal plasma cells express CD45, CD45RA, but most myeloma cells do not express CD45 and a small subpopulation of myeloma cells express CD45, CD45R0 but not CD45RA. Myeloma cells respond to interleukin 6(IL-6) to proliferate, and this IL-6-induced proliferation of myeloma cells requires CD45, CD45R0 on their surface. In order to clarify the role of CD45 (CD45R0) on the IL-6-induced proliferation, we investigated how CD45R0 or CD45RA translocated to lipid rafts after IL-6 stimulation in human myeloma cell lines. CD45R0 rapidly translocated to lipid rafts after IL-6 stimulation, while CD45RA remained outside of lipd rafts. The presence of CD45RA induced the suppression of intracellular signaling induced by IL-6, especially the downregulation of phosphorylation of ERK. Also, we investigated what molecules could bind to CD45RA but not CD45R0 extracellularly ; Galectin-1 could bind to CD45RA but not CD45RO, and induced the suppression of IL-6-induced proliferation. Therefore, these results suggest that IL-6-induced proliferation of myeloma cells is regulated by CD45RO, and CD45RA has the inhibitory effect on IL-6-induced proliferation and the mechanism of the inhibitory effect of CD45RA may be due to the blockade of translocation to lipid rafts and the extracellualr binding of Galectin-1.

人骨髓瘤细胞与诺玛骨髓浆细胞中的表面抗原表达不同。尤其是，所有正常的浆细胞表达CD45，CD45RA，但大多数骨髓瘤细胞均未表达CD45，并且骨髓瘤细胞的小亚群表达CD45，CD45R0，但不能表达CD45RA。骨髓瘤细胞对白介素6（IL-6）的反应以增殖，这种IL-6诱导的骨髓瘤细胞的增殖需要CD45，CD45R0在其表面上。为了阐明CD45（CD45R0）在IL-6诱导的增殖中的作用，我们研究了在人骨髓瘤细胞系中IL-6刺激后，CD45R0或CD45RA如何转移到脂质筏。 CD45R0在IL-6刺激后迅速转移到脂质筏上，而CD45RA仍留在Lipd筏外。 CD45RA的存在引起了IL-6诱导的细胞内信号传导的抑制，尤其是ERK磷酸化的下调。另外，我们研究了哪些分子可以与CD45RA结合，但不与CD45R0结合。 Galectin-1可以与CD45RA结合，但不能结合CD45RO，并诱导IL-6诱导的增殖。因此，这些结果表明，IL-6诱导的骨髓瘤细胞的增殖受CD45RO的调节，CD45RA对IL-6诱导的增殖具有抑制作用，并且CD45RA的抑制作用的机制可能是由于对脂质Rafts的易位易位抗脂肪和外层纤维素结合的封锁。

项目成果

Heterogeneous expression of CD32 and CD32-mediated growth suppression in human myeloma cells.

人骨髓瘤细胞中 CD32 的异质表达和 CD32 介导的生长抑制。

• 发表时间: 2006
• 期刊: Haematologica 91
• 作者: Harada H;et al.;Zheng X
• 通讯作者: Zheng X

A rapid translocation of CD45RO but not CD45RA to lipid rafts in IL-6-induced proliferation in myeloma

IL-6诱导的骨髓瘤增殖中CD45RO而非CD45RA快速易位至脂筏

• 发表时间: 2005
• 期刊: Blood 105・8
• 作者: 山崎雅英;舟田久;Fu-Jun Li
• 通讯作者: Fu-Jun Li

三輪血液病学

三和血液学

• 发表时间: 2005
• 作者: 共同執筆 浅野茂隆;池田康夫;内山卓
• 通讯作者: 内山卓

An increased in MPC-1-and MPC-1-CD45+ immature myeloma cells in the progressive states of bone marrow plasmacytosis.

在骨髓浆细胞增多的进展状态下，MPC-1-和 MPC-1-CD45 未成熟骨髓瘤细胞增加。

• 发表时间: 2006
• 期刊: Int J Hematol 83
• 作者: 片山直之;珠玖洋;Shangqin Liu;Norinaga Urahama;Tsuneyoshi N;Otsuyama K
• 通讯作者: Otsuyama K

A rapid translocation of CD45RO but not CD45RA to lipid rafts in IL-6-induced proliferation in myeloma.

在 IL-6 诱导的骨髓瘤增殖中，CD45RO（而非 CD45RA）快速易位至脂筏。

• 发表时间: 2005
• 期刊: Blood 105
• 作者: 山崎雅英;船田久;Hideaki Ishikawa;Zheng X;Imayoshi M;Katsuya Yamamoto;金倉 譲ほか;Shangqin Liu;原田浩徳 他;Katsuya Yamamoto;Liu S;Kohara J.;山崎雅英;原田結花 他;Hideaki Ishikawa;山崎雅英;Li F
• 通讯作者: Li F