Glioblastoma recurrence correlates with NLGN3 levels.

Glioblastoma recurrence correlates with NLGN3 levels.
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胶质母细胞瘤复发与 NLGN3 水平相关

DOI:
10.1002/cam4.1538
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发表时间:
2018-07
期刊:
影响因子:
4
通讯作者:
Wan Q
Wan Q
中科院分区:
医学3区
文献类型:
--
作者:
Liu R;Qin XP;Zhuang Y;Zhang Y;Liao HB;Tang JC;Pan MX;Zeng FF;Lei Y;Lei RX;Wang S;Liu AC;Chen J;Zhang ZF;Zhao D;Wu SL;Liu RZ;Wang ZF;Wan Q

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胶质母细胞瘤(GBM)是脑中最具侵袭性的胶质瘤。GBM在肿瘤切除后的短期内复发几乎是不可避免的。在2013年至2016年收集的386例GBM病例的回顾性研究中,我们发现GBM的复发主要发生在脑深部区域,包括基底节,丘脑和胼胝体。但这种现象背后的机制尚不清楚。以前的研究表明,神经连接素-3(NLGN 3)是GBM生长所必需的。我们的研究结果表明,在正常人脑中,皮层中的NLGN 3水平高于深层区域,在正常小鼠大脑中也发现了类似的模式。相反,GBM患者的脑深部区域中的NLGN 3水平很高。我们还表明,NLGN 3浓度的增加促进了U251细胞和U87-MG细胞的生长。分别使用含DMEM的皮质神经元培养基(C-NCM)和基底节神经元培养基(BG-NCM)培养从患者分离的U251、U87-MG和GBM细胞,我们发现这些细胞经C-NCM和BG-NCM处理后生长更快,其中C-NCM处理的细胞生长速度快于BG-NCM处理的细胞。通过ADAM 10 i抑制NLGN 3释放可防止NCM诱导的细胞生长。总之,这项研究表明,在GBM病理情况下,脑深部区域中NLGN 3水平的增加可能有助于基底神经节、丘脑和胼胝体中的GBM复发。
Glioblastoma (GBM) is the most aggressive glioma in the brain. Recurrence of GBM is almost inevitable within a short term after tumor resection. In a retrospective study of 386 cases of GBM collected between 2013 and 2016, we found that recurrence of GBM mainly occurs in the deep brain regions, including the basal ganglia, thalamus, and corpus callosum. But the mechanism underlying this phenomenon is not clear. Previous studies suggest that neuroligin‐3 (NLGN3) is necessary for GBM growth. Our results show that the levels of NLGN3 in the cortex are higher than those in the deep regions in a normal human brain, and similar patterns are also found in a normal mouse brain. In contrast, NLGN3 levels in the deep brain regions of GBM patients are high. We also show that an increase in NLGN3 concentration promotes the growth of U251 cells and U87‐MG cells. Respective use of the cortex neuron culture medium (C‐NCM) and basal ganglia neuron culture medium (BG‐NCM) with DMEM to cultivate U251, U87‐MG and GBM cells isolated from patients, we found that these cells grew faster after treatment with C‐NCM and BG‐NCM in which the cells treated with C‐NCM grew faster than the ones treated with BG‐NCM group. Inhibition of NLGN3 release by ADAM10i prevents NCM‐induced cell growth. Together, this study suggests that increased levels of NLGN3 in the deep brain region under the GBM pathological circumstances may contribute to GBM recurrence in the basal ganglia, thalamus, and corpus callosum.
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