BAFF is involved in macrophage-induced bortezomib resistance in myeloma.
BAFF is involved in macrophage-induced bortezomib resistance in myeloma.
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BAFF 参与骨髓瘤中巨噬细胞诱导的硼替佐米耐药性。
DOI：
10.1038/cddis.2017.533
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发表时间：
2017-11-02
影响因子：
9
通讯作者：
Cai Z
中科院分区：
文献类型：
--
作者：
Chen J;He D;Chen Q;Guo X;Yang L;Lin X;Li Y;Wu W;Yang Y;He J;Zhang E;Yi Q;Cai Z
我们的目的是表征 B 细胞激活因子 (BAFF) 在巨噬细胞介导的多发性骨髓瘤 (MM) 细胞对硼替佐米 (bort) 耐药中的作用，并进一步了解该过程中涉及的分子机制。首先，我们使用定量逆转录聚合酶链反应和流式细胞术检测骨髓瘤细胞和巨噬细胞上的 BAFF 及其三种受体。在 MM 患者、MM 细胞系和巨噬细胞中测试了 BAFF 的分泌。在共培养系统中使用 BAFF 中和抗体或用小干扰 RNA 敲低巨噬细胞中 BAFF 的表达，可显着减弱巨噬细胞保护 MM 细胞免受 bort 诱导的细胞凋亡的能力。我们还表明，MM-巨噬细胞通过 BAFF 及其受体的相互作用主要是由 Src、Erk1/2、Akt 和核因子 kappa B 信号传导的激活以及 bort 诱导的 caspase 激活的抑制介导的。我们的数据表明，BAFF 在巨噬细胞介导的 MM 细胞对 bort 的抵抗中发挥了功能性作用，这表明靶向 BAFF 可能为分子和免疫靶向治疗方法提供基础。
We aimed to characterize the role of B-cell activating factor (BAFF) in macrophage-mediated resistance of multiple myeloma (MM) cells to bortezomib (bort), and to further understand the molecular mechanisms involved in the process. First, we detected BAFF and its three receptors on myeloma cells and macrophages using the quantitative reverse transcriptase-polymerase chain reaction and flow cytometry. The secretion of BAFF was tested in patients with MM, MM cell lines, and macrophages. The ability of macrophages to protect MM cells from bort-induced apoptosis was significantly attenuated using BAFF-neutralizing antibody in the co-culture system or knocking down the expression of BAFF in macrophages with small interfering RNA. We also showed that the MM–macrophage interaction through BAFF and its receptors was primarily mediated by the activation of Src, Erk1/2, Akt, and nuclear factor kappa B signaling and the suppression of caspase activation induced by bort. Our data demonstrated that BAFF played a functional role in the macrophage-mediated resistance of MM cells to bort, suggesting that targeting BAFF may provide a basis for the molecular- and immune-targeted therapeutic approach.
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影响因子：
12.8
作者：
Hengeveld PJ;Kersten MJ
通讯作者：
Kersten MJ
影响因子：
3.1
作者：
Almendras, Carmen P. Montano;Thudium, Christian S.;Richter, Johan
通讯作者：
Richter, Johan
影响因子：
4.3
作者：
Jaguin, Marie;Houlbert, Noemie;Lecureur, Valerie
通讯作者：
Lecureur, Valerie
影响因子：
--
作者：
Demchenko YN;Kuehl WM
通讯作者：
Kuehl WM
影响因子：
5.2
作者：
Fairfield H;Falank C;Avery L;Reagan MR
通讯作者：
Reagan MR