Rooj Arun K, Mineo Marco, Godlewski Jakub
Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, 4 Blackfan Circle, Boston, MA, 02115, USA.
Brain Tumor Pathol. 2016 Apr;33(2):77-88. doi: 10.1007/s10014-016-0259-3. Epub 2016 Mar 11.
To promote the tumor growth, angiogenesis, metabolism, and invasion, glioblastoma (GBM) cells subvert the surrounding microenvironment by influencing the endogenous activity of other brain cells including endothelial cells, macrophages, astrocytes, and microglia. Large number of studies indicates that the intra-cellular communication between the different cell types of the GBM microenvironment occurs through the functional transfer of oncogenic components such as proteins, non-coding RNAs, DNA and lipids via the release and uptake of extracellular vesicles (EVs). Unlike the communication through the secretion of chemokines and cytokines, the transfer and gene silencing activity of microRNAs through EVs is more complex as the biogenesis and proper packaging of microRNAs is crucial for their uptake by recipient cells. Although the specific mechanism of EV-derived microRNA uptake and processing in recipient cells is largely unknown, the screening, identifying and finally targeting of the EV-associated pro-tumorigenic microRNAs are emerging as new therapeutic strategy to combat the GBM.
为促进肿瘤生长、血管生成、代谢和侵袭，胶质母细胞瘤（GBM）细胞通过影响包括内皮细胞、巨噬细胞、星形胶质细胞和小胶质细胞在内的其他脑细胞的内源性活性来颠覆周围的微环境。大量研究表明，GBM微环境中不同细胞类型之间的细胞内通讯是通过致癌成分（如蛋白质、非编码RNA、DNA和脂质）通过细胞外囊泡（EVs）的释放和摄取进行功能转移来实现的。与通过趋化因子和细胞因子分泌进行的通讯不同，通过EVs进行的微小RNA的转移和基因沉默活性更为复杂，因为微小RNA的生物合成和正确包装对于其被受体细胞摄取至关重要。尽管EV衍生的微小RNA在受体细胞中的摄取和加工的具体机制在很大程度上尚不清楚，但筛选、鉴定并最终靶向与EV相关的促肿瘤微小RNA正成为对抗GBM的新治疗策略。
