Medical Research Council Centre for Inflammation Research at the University of Edinburgh, The Queen's Medical Research Institute, Edinburgh, United Kingdom.
Front Immunol. 2018 May 23;9:1111. doi: 10.3389/fimmu.2018.01111. eCollection 2018.
Cells undergoing apoptosis produce heterogeneous populations of membrane delimited extracellular vesicles (Apo-EVs) which vary not only in size-from tens of nanometers to several microns-but also in molecular composition and cargo. Apo-EVs carry a variety of potentially biologically active components, including small molecules, proteins, and nucleic acids. Larger forms of Apo-EVs, commonly termed "apoptotic bodies," can carry organelles, such as mitochondria and nuclear fragments. Molecules displayed on the surface of extracellular vesicles (EVs) can contribute substantially to their size, as well as their functions. Thus far, relatively little is known of the functional significance of Apo-EVs apart from their roles in fragmentation of dying cells and indicated immunomodulatory activities. Here, we discuss EV production by dying tumor cells and consider the possible roles of Apo-EVs in a cell death-driven sector of the tumor microenvironment known as the onco-regenerative niche (ORN). We propose that tumor-derived Apo-EVs are significant vehicles of the ORN, functioning as critical intercellular communicators that activate oncogenic tissue repair and regeneration pathways. We highlight important outstanding questions and suggest that Apo-EVs may harbor novel therapeutic targets.
凋亡细胞产生异质群体的膜性细胞外囊泡（凋亡 EVs），其不仅大小不一（从数十纳米到数微米），而且分子组成和货物也不同。凋亡 EVs 携带多种潜在的生物活性成分，包括小分子、蛋白质和核酸。较大形式的凋亡 EVs，通常称为“凋亡体”，可以携带细胞器，如线粒体和核片段。细胞外囊泡（EVs）表面显示的分子对其大小及其功能有重要贡献。到目前为止，除了在垂死细胞的碎片化和指示免疫调节活性方面的作用外，人们对凋亡 EVs 的功能意义知之甚少。在这里，我们讨论了垂死肿瘤细胞产生 EV 的情况，并考虑了凋亡 EVs 在肿瘤微环境中一个称为癌再生龛（ORN）的细胞死亡驱动区域中的可能作用。我们提出肿瘤衍生的凋亡 EVs 是 ORN 的重要载体，作为关键的细胞间通讯器，激活致癌组织修复和再生途径。我们强调了重要的悬而未决的问题，并提出凋亡 EVs 可能具有新的治疗靶点。
