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Temozolomide affects Extracellular Vesicles Released by Glioblastoma Cells
Biochimie ( IF 3.9 ) Pub Date : 2018-02-15 , DOI: 10.1016/j.biochi.2018.02.007
Gwennan André-Grégoire , Nicolas Bidère , Julie Gavard

Glioblastoma multiforme (GBM) is the most aggressive primary tumour within the brain as well as the most common and lethal cerebral cancer, mainly because of treatment failure. Indeed, tumour recurrence is inevitable and fatal in a short period of time. Glioblastoma stem-like cells (GSCs) are thought to participate in tumour initiation, expansion, resistance to treatments, including to the alkylating chemotherapeutic agent temozolomide, and relapse. Here, we assessed whether extracellular vesicles (EVs) released by GSCs could disseminate factors involved in resistance mechanisms. We first characterized EVs either circulating in peripheral blood from newly diagnosed patients or released by patient-derived temozolomide-resistant GSCs. We found that EVs from both sources were mainly composed of particles homogeneous in size (50–100 nm), while they were more abundant in liquid biopsies from GBM patients, as compared to healthy donors. Further, mass spectrometry analysis from GSC-derived EVs unveiled that particles from control and temozolomide-treated cells share core components of EVs, as well as ribosome- and proteasome-associated networks. More strikingly, temozolomide treatment led to the enrichment of EVs with cargoes dedicated to cell adhesion processes. Thus, while relatively inefficient in killing GSCs in vitro, temozolomide could instead increase the release of pro-tumoral information.



中文翻译:

替莫唑胺影响胶质母细胞瘤细胞释放的细胞外囊泡

多形性胶质母细胞瘤(GBM)是大脑中最具有侵略性的原发肿瘤,也是最常见和致命的脑癌,主要是因为治疗失败。实际上,在短时间内肿瘤复发是不可避免的并且是致命的。胶质母细胞瘤干样细胞(GSC)被认为参与肿瘤的发生,扩展,对治疗的耐药性,包括对烷基化化疗剂替莫唑胺的治疗以及复发。在这里,我们评估了GSCs释放的细胞外囊泡(EV)是否可以传播参与耐药机制的因素。我们首先对电动汽车的特征进行了描述,这些电动汽车是在新诊断的患者的外周血中循环或由患者产生的抗替莫唑胺的GSC释放。我们发现两种来源的电动汽车主要由尺寸均一(50–100 nm)的颗粒组成,与健康捐献者相比,他们在GBM患者的液体活检中含量更高。此外,来自GSC的电动汽车的质谱分析揭示,来自对照和替莫唑胺处理的细胞的颗粒共享电动汽车的核心组件,以及与核糖体和蛋白酶体相关的网络。更引人注目的是,替莫唑胺处理导致电动汽车充斥着专门用于细胞粘附过程的货物。因此,虽然杀死GSC的效率相对较低 替莫唑胺处理导致电动汽车充斥着专门用于细胞粘附过程的货物。因此,虽然杀死GSC的效率相对较低 替莫唑胺治疗导致电动汽车充斥着专门用于细胞粘附过程的货物。因此,虽然杀死GSC的效率相对较低在体外,替莫唑胺可以增加促肿瘤信息的释放。

更新日期:2018-02-15
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