Regulatory mechanism of membrane coreceptors in the proliferation of human myeloma cells

膜辅助受体对人骨髓瘤细胞增殖的调控机制

基本信息

批准号：
14370305
负责人：
KAWANO Michio
金额：
$ 7.55万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370305/
关键词：
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

项目摘要

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.

在多发性骨髓瘤中，与正常浆细胞相比，膜蛋白的表面表达有很大的差异。尤其是，数量受限的骨髓瘤细胞表达CD45分子和CD45RO，而正常的浆细胞表达CD45和CD45RA。此外，可以对IL-6进行反应以增殖的骨髓瘤细胞是CD45阳性（CD45+）未成熟的骨髓瘤细胞，而CD45阴性（CD45-）骨髓瘤细胞无法响应IL-6来增殖。在这项研究中，我们试图阐明CD45分子在人类诱导的人群中的作用，以阐明人类在人类中的作用，这些细胞在人类诱导的人群中的作用，在人类诱导的蛋白酶中的作用。 IL-6刺激后的CD45同工型。从这项研究中，我们发现位于没有IL-6刺激的脂质筏外的CD45分子，但是IL-6刺激CD45RO，但没有CD45RA迅速移至脂质筏。此外，我们证实了CD45RO分子通过lyn的Tyr507的去磷酸化作为LYN的活化剂的CD45RO分子。这些结果可以解释为什么CD45+骨髓瘤细胞（CD45RO+）而不是正常的浆细胞（CD45RA+）可以响应IL-6以增殖。将来，这些结果也有助于人骨髓瘤分子靶疗法的进步。