PDF(Pubmed)
Abstract：
Extracellular vesicles (EVs) are a new mechanism of cellular communication, by delivering their cargo into target cells to modulate molecular pathways. EV-mediated crosstalk contributes to tumor survival and resistance to cellular stress. However, the role of EVs in B-cell Acute Lymphoblastic Leukaemia (B-ALL) awaits to be thoroughly investigated. We recently published that ActivinA increases intracellular calcium levels and promotes actin polymerization in B-ALL cells. These biological processes guide cytoskeleton reorganization, which is a crucial event for EV secretion and internalization. Hence, we investigated the role of EVs in the context of B-ALL and the impact of ActivinA on this phenomenon. We demonstrated that leukemic cells release a higher number of EVs in response to ActivinA treatment, and they can actively uptake EVs released by other B-ALL cells. Under culture-induced stress conditions, EVs coculture promoted cell survival in B-ALL cells in a dose-dependent manner. Direct stimulation of B-ALL cells with ActivinA or with EVs isolated from ActivinA-stimulated cells was even more effective in preventing cell death. This effect can be possibly ascribed to the increase of vesiculation and modifications of EV-associated microRNAs induced by ActivinA. These data demonstrate that ActivinA boosts EV-mediated B-ALL crosstalk, improving leukemia survival in stress conditions.
摘要：
细胞外囊泡(EV)是一种新的细胞通讯机制,通过将它们的货物递送到靶细胞中来调节分子途径。EV介导的串扰有助于肿瘤存活和对细胞应激的抵抗。然而,EVs在B细胞急性淋巴细胞白血病(B-ALL)中的作用有待深入研究.我们最近发表了ActivinA增加细胞内钙水平并促进B-ALL细胞中的肌动蛋白聚合。这些生物过程指导细胞骨架重组，这是EV分泌和内化的关键事件。因此，我们调查了EV在B-ALL中的作用以及ActivinA对这一现象的影响.我们证明了白血病细胞响应ActivinA治疗释放更多的EV，它们可以主动摄取其他B-ALL细胞释放的电动汽车。在培养诱导的胁迫条件下，EV共培养以剂量依赖性方式促进B-ALL细胞的细胞存活。用ActivinA或用从ActivinA刺激的细胞分离的EV直接刺激B-ALL细胞在预防细胞死亡方面甚至更有效。这种作用可能归因于由ActivinA诱导的EV相关microRNA的囊泡形成和修饰的增加。这些数据表明，ActivinA增强了EV介导的B-ALL串扰，提高白血病在应激条件下的生存率。
