Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression.
Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression.
复制标题
DOI：
10.3389/fimmu.2018.00738
复制
发表时间：
2018
影响因子：
7.3
通讯作者：
Vader P
中科院分区：
文献类型：
--
作者：
Willms E;Cabañas C;Mäger I;Wood MJA;Vader P
细胞释放出膜封闭的纳米大小的囊泡，称为细胞外囊泡（EV），通过在细胞之间传递生物信息来充当细胞间通讯的介导剂。肿瘤衍生的EV已经成为癌症发展和进展中的重要介质，主要通过转移其生物活性内容物，所述生物活性内容物可以包括癌蛋白、癌基因、趋化因子受体以及可溶性因子、参与血管生成或炎症的蛋白质和miRNA的转录物。这种转移已被证明会影响原发性肿瘤的转移行为。此外，肿瘤衍生的EV已被证明会影响远处的细胞小生境，建立有利的微环境，支持播散的癌细胞在到达这些转移前小生境时的生长。通常认为，细胞释放许多具有不同生物物理特性和生物功能的主要EV群体。外泌体、微泡和凋亡小体是最广泛研究和表征的EV群体。它们主要基于其细胞内起源而被区分。然而，越来越多的证据表明，即使在这些EV人群中，也可能存在各种亚群。这种异质性在EV生物学和功能的研究中引入了额外的复杂性。例如，EV亚群可能在癌症生物学基础的复杂生物学过程中发挥独特作用。在这里，我们讨论了关于EV亚群在癌症发展和进展中的作用的现有知识，并强调了EV异质性的相关性。四跨膜蛋白和整合素在其中的位置将被强调。由于解决EV异质性已成为EV领域的关键，目前和新的技术分离EV亚群也将进行讨论。对EV异质性的进一步剖析将促进我们对EV在健康和疾病中的关键作用的理解。
Cells release membrane enclosed nano-sized vesicles termed extracellular vesicles (EVs) that function as mediators of intercellular communication by transferring biological information between cells. Tumor-derived EVs have emerged as important mediators in cancer development and progression, mainly through transfer of their bioactive content which can include oncoproteins, oncogenes, chemokine receptors, as well as soluble factors, transcripts of proteins and miRNAs involved in angiogenesis or inflammation. This transfer has been shown to influence the metastatic behavior of primary tumors. Moreover, tumor-derived EVs have been shown to influence distant cellular niches, establishing favorable microenvironments that support growth of disseminated cancer cells upon their arrival at these pre-metastatic niches. It is generally accepted that cells release a number of major EV populations with distinct biophysical properties and biological functions. Exosomes, microvesicles, and apoptotic bodies are EV populations most widely studied and characterized. They are discriminated based primarily on their intracellular origin. However, increasing evidence suggests that even within these EV populations various subpopulations may exist. This heterogeneity introduces an extra level of complexity in the study of EV biology and function. For example, EV subpopulations could have unique roles in the intricate biological processes underlying cancer biology. Here, we discuss current knowledge regarding the role of subpopulations of EVs in cancer development and progression and highlight the relevance of EV heterogeneity. The position of tetraspanins and integrins therein will be highlighted. Since addressing EV heterogeneity has become essential for the EV field, current and novel techniques for isolating EV subpopulations will also be discussed. Further dissection of EV heterogeneity will advance our understanding of the critical roles of EVs in health and disease.