van Dongen Helena M, Masoumi Niala, Witwer Kenneth W, Pegtel D Michiel
Department of Pathology, Exosomes Research Group, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Microbiol Mol Biol Rev. 2016 Mar 2;80(2):369-86. doi: 10.1128/MMBR.00063-15. Print 2016 Jun.
Extracellular vesicles (EVs) have emerged as crucial mediators of intercellular communication, being involved in a wide array of key biological processes. Eukaryotic cells, and also bacteria, actively release heterogeneous subtypes of EVs into the extracellular space, where their contents reflect their (sub)cellular origin and the physiologic state of the parent cell. Within the past 20 years, presumed subtypes of EVs have been given a rather confusing diversity of names, including exosomes, microvesicles, ectosomes, microparticles, virosomes, virus-like particles, and oncosomes, and these names are variously defined by biogenesis, physical characteristics, or function. The latter category, functions, in particular the transmission of biological signals between cells in vivo and how EVs control biological processes, has garnered much interest. EVs have pathophysiological properties in cancer, neurodegenerative disorders, infectious disease, and cardiovascular disease, highlighting possibilities not only for minimally invasive diagnostic applications but also for therapeutic interventions, like macromolecular drug delivery. Yet, in order to pursue therapies involving EVs and delivering their cargo, a better grasp of EV targeting is needed. Here, we review recent progress in understanding the molecular mechanisms underpinning EV uptake by receptor-ligand interactions with recipient cells, highlighting once again the overlap of EVs and viruses. Despite their highly heterogeneous nature, EVs require common viral entry pathways, and an unanticipated specificity for cargo delivery is being revealed. We discuss the challenges ahead in delineating specific roles for EV-associated ligands and cellular receptors.
细胞外囊泡（EVs）已成为细胞间通讯的关键介质，参与了一系列重要的生物学过程。真核细胞以及细菌都会主动将异质性的EV亚型释放到细胞外空间，其内容物反映了它们的（亚）细胞来源和母细胞的生理状态。在过去20年里，假定的EV亚型被赋予了相当繁杂多样的名称，包括外泌体、微囊泡、胞外体、微粒、病毒体、病毒样颗粒和肿瘤小体等，这些名称根据生物发生、物理特性或功能有不同的定义。后者，即功能，特别是体内细胞间生物信号的传递以及EVs如何控制生物学过程，引起了人们极大的兴趣。EVs在癌症、神经退行性疾病、传染病和心血管疾病中具有病理生理特性，这不仅凸显了其在微创诊断应用方面的可能性，也为治疗干预（如大分子药物递送）提供了可能。然而，为了开展涉及EVs及其所载物的治疗，需要更好地掌握EVs的靶向作用。在此，我们回顾了在理解受体 - 配体相互作用介导EVs被受体细胞摄取的分子机制方面的最新进展，再次强调了EVs与病毒的重叠之处。尽管EVs具有高度异质性，但它们需要共同的病毒进入途径，并且正在揭示出其在货物递送方面出人意料的特异性。我们讨论了在确定EV相关配体和细胞受体的具体作用方面面临的挑战。
