Expression and function of chemokine receptors in human multiple myeloma
Expression and function of chemokine receptors in human multiple myeloma
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DOI：
10.1038/sj.leu.2402717
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发表时间：
2003-01-01
期刊：
影响因子：
11.4
通讯作者：
Nilsson, G
中科院分区：
文献类型：
--
作者：
Möller, C;Strömberg, T;Nilsson, G
多发性骨髓瘤（MM）是一种选择性发生于骨髓的B细胞肿瘤。促进多发性骨髓瘤细胞募集到骨髓微环境的机制还不清楚。趋化因子在淋巴细胞运输和归巢中起着重要作用。在这项研究中，我们研究了MM衍生细胞系和原代MM细胞中趋化因子受体的表达和功能重要性。我们发现MM细胞系表达功能性CCR 1、CXCR 3和CXCR 4受体，有些还表达CCR 6。尽管只有少数细胞系对钙有反应。在激动剂刺激后的动员中，分别在5/6和4/6的测试细胞系中获得了对CCR 1配体RANTES和MIP-1 α的迁移反应。6个细胞系中有5个显示出对CXCR 4配体SDF-1的应答。此外，3/6的细胞系响应MIP-3 α和IP-10（分别为CCR 6和CXCR 3的配体）而迁移。还在原代MM细胞中证实了CXCR 4和CCR 1的表达及其分别向其配体SDF-1、RANTES和MIP-1a的迁移。这些发现表明，趋化因子受体表达和MM细胞迁移到其配体的能力与骨髓中MM细胞的区室化有关。
Multiple myeloma (MM) is a B cell tumor characterized by its sellective localization in the bone marrow. The mechanisms that contribute to the multiple myeloma cell recruitment to the bone marrow microenvironment are not well understood. Chemokines play a central role for lymphocyte trafficking and homing. In this study we have investigated expression and functional importance of chemokine receptors in MM-derived cell lines and primary MM cells. We found that MM cell lines express functional CCR1, CXCR3 and CXCR4 receptors, and some also CCR6. Although only a minority of the cell lines responded by calcium. mobilization after agonist stimulation, a migratory response to the CCR1 ligands RANTES and MIP-1alpha was obtained in 5/6 and 4/6, respectively, of the cell lines tested. Five out of six cell lines showed a response to the CXCR4 ligand SDF-1. In addition, 3/6 cell lines migrated in response to MIP-3alpha and IP-10, ligands for CCR6 and CXCR3, respectively. The expression of CXCR4 and CCR1 and the migration to their ligands, SDF-1, and RANTES and MIP-1a, respectively, were also demonstrated in primary MM cells. These findings suggest that chemolkine receptor expression and the migratory capacity of MM cells to their ligands are relevant for the compartmentalization of MM cells in the bone marrow.