CsD163, a novel therapeutic target, regulates the proliferation and stemness of glioma cells via casein kinase 2
CsD163, a novel therapeutic target, regulates the proliferation and stemness of glioma cells via casein kinase 2
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CD163 是一种新型治疗靶点，通过酪蛋白激酶 2 调节神经胶质瘤细胞的增殖和干性
DOI：
10.1038/s41388-018-0515-6
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发表时间：
2019-02-21
期刊：
影响因子：
8
通讯作者：
Ke, Yiquan
中科院分区：
文献类型：
--
作者：
Chen, Taoliang;Chen, Jiansheng;Ke, Yiquan
神经胶质瘤是一种毁灭性的癌症，预后不佳，迫切需要发现新的神经胶质瘤特异性抗原用于神经胶质瘤治疗。先前的研究已在某些实体瘤中鉴定出 CD163 阳性肿瘤细胞，但神经胶质瘤中的 CD163 表达仍不清楚。在这项研究中，通过对公共数据集的分析，我们证明了神经胶质瘤标本中 CD163 的过度表达与患者不良预后相关。 CD163 表达在神经胶质瘤细胞中增加，尤其是原代神经胶质瘤细胞。 CD163 表达的丧失抑制了多形性胶质母细胞瘤 (GBM) 细胞系和原代胶质瘤细胞的细胞周期进展和增殖。 CD163 直接与酪蛋白激酶 2 (CK2) 相互作用，并且 CD163 沉默可通过 CK2 降低 AKT/GSK3β/β-catenin/cyclin D1 通路活性。此外，CD163在CD133阳性胶质瘤干细胞（GSC）中上调，CD163下调会降低GSC标志物的表达，包括CD133、ALDH1A1、NANOG和OCT4。 CD163 的敲低通过抑制 CK2/AKT/GSK3β/β-连环蛋白途径来损害 GSC 干性。最后，CD163 抗体成功诱导针对神经胶质瘤细胞的补体依赖性细胞毒性。我们的研究结果表明，CD163 通过 CK2 促进神经胶质瘤发生，并提供了 CD163 和 CD163 通路可能作为神经胶质瘤治疗靶点的临床前证据。
Glioma is a devastating cancer with a dismal prognosis and there is an urgent need to discover novel glioma-specific antigens for glioma therapy. Previous studies have identified CD163-positive tumour cells in certain solid tumours, but CD163 expression in glioma remains unknown. In this study, via an analysis of public datasets, we demonstrated that CD163 overexpression in glioma specimens correlated with an unfavourable patient prognosis. CD163 expression was increased in glioma cells, especially primary glioma cells. The loss of CD163 expression inhibited both cell cycle progression and the proliferation of glioblastoma multiforme (GBM) cell lines and primary glioma cells. CD163 interacted directly with casein kinase 2 (CK2) and CD163 silencing reduced AKT/GSK3β/β-catenin/cyclin D1 pathway activity via CK2. Moreover, CD163 was upregulated in CD133-positive glioma stem cells (GSCs), and CD163 downregulation decreased the expression of GSC markers, including CD133, ALDH1A1, NANOG and OCT4. The knockdown of CD163 impaired GSC stemness by inhibiting the CK2/AKT/GSK3β/β-catenin pathway. Finally, a CD163 antibody successfully induced complement-dependent cytotoxicity against glioma cells. Our findings indicate that CD163 contributes to gliomagenesis via CK2 and provides preclinical evidence that CD163 and the CD163 pathway might serve as a therapeutic target for glioma.