Ung Timothy H, Madsen Helen J, Hellwinkel Justin E, Lencioni Alex M, Graner Michael W
Department of Neurosurgery, University of Colorado School of Medicine, Aurora, Colorado, USA.
Cancer Sci. 2014 Nov;105(11):1384-92. doi: 10.1111/cas.12534. Epub 2014 Oct 9.
Exosomes are virus-sized, membrane-enclosed vesicles with origins in the cellular endosomal system, but are released extracellularly. As a population, these tiny vesicles carry relatively enormous amounts of information in their protein, lipid and nucleic acid content, and the vesicles can have profound impacts on recipient cells. This review employs publically-available data combined with gene ontology applications to propose a novel concept, that exosomes transport transcriptional and translational machinery that may have direct impacts on gene expression in recipient cells. Here, we examine the previously published proteomic contents of medulloblastoma-derived exosomes, focusing on transcriptional regulators; we found that there are numerous proteins that may have potential roles in transcriptional and translational regulation with putative influence on downstream, cancer-related pathways. We expanded this search to all of the proteins in the Vesiclepedia database; using gene ontology approaches, we see that these regulatory factors are implicated in many of the processes involved in cancer initiation and progression. This information suggests that some of the effects of exosomes on recipient cells may be due to the delivery of protein factors that can directly and fundamentally change the transcriptional landscape of the cells. Within a tumor environment, this has potential to tilt the advantage towards the cancer.
外泌体是病毒大小的、被膜包裹的囊泡，起源于细胞内体系统，但释放到细胞外。总体而言，这些微小的囊泡在其蛋白质、脂质和核酸成分中携带了相对大量的信息，并且这些囊泡可对受体细胞产生深远影响。本综述利用公开可得的数据并结合基因本体应用，提出了一个新颖的概念，即外泌体运输转录和翻译机制，这可能对受体细胞中的基因表达产生直接影响。在此，我们研究了先前发表的髓母细胞瘤来源外泌体的蛋白质组内容，重点关注转录调节因子；我们发现有许多蛋白质可能在转录和翻译调控中具有潜在作用，并对下游与癌症相关的途径具有推定影响。我们将此搜索扩展到Vesiclepedia数据库中的所有蛋白质；使用基因本体方法，我们发现这些调节因子与癌症发生和进展所涉及的许多过程有关。这一信息表明，外泌体对受体细胞的一些影响可能是由于蛋白质因子的传递，这些因子可直接且从根本上改变细胞的转录格局。在肿瘤环境中，这有可能使优势向癌症倾斜。
