Lau Nicolas Cheuk Hang, Yam Judy Wai Ping
Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong.
Cancers (Basel). 2023 Mar 27;15(7):1992. doi: 10.3390/cancers15071992.
Exosomes are mediators of intercellular communication in normal physiology and diseases. While many studies have emerged on the function of exosomal cargoes, questions remain regarding the origin of these exosomes. The packaging and secretion of exosomes in different contexts modify exosomal composition, which may in turn impact delivery, uptake and cargo function in recipient cells. A mechanistic understanding of exosome biology is therefore crucial to investigating exosomal function in complex biological systems and to the development of novel therapeutic approaches. Here, we outline the steps in exosome biogenesis, including endosome formation, MVB formation, cargo sorting and extracellular release, as well as exosome absorption, including targeting, interaction with recipient cells and the fate of internalized exosomes. In addition to providing a framework of exosome dynamics, we summarize current evidence on major pathways and regulatory mechanisms. We also highlight the various mechanisms observed in cancer and point out directions to improve study design in exosome biology. Further research is needed to illuminate the relationship between exosome biogenesis and function, which will aid the development of translational applications.
外泌体是正常生理和疾病中细胞间通讯的介质。虽然关于外泌体货物功能的研究已经很多，但这些外泌体的起源仍存在疑问。不同背景下外泌体的包装和分泌会改变外泌体的组成，这反过来可能会影响其在受体细胞中的递送、摄取和货物功能。因此，对外泌体生物学的机制性理解对于研究复杂生物系统中的外泌体功能以及开发新的治疗方法至关重要。在这里，我们概述了外泌体生物发生的步骤，包括内体形成、多泡体形成、货物分选和细胞外释放，以及外泌体吸收，包括靶向、与受体细胞的相互作用和内化外泌体的命运。除了提供外泌体动力学的框架外，我们还总结了关于主要途径和调节机制的现有证据。我们还强调了在癌症中观察到的各种机制，并指出了改进外泌体生物学研究设计的方向。需要进一步的研究来阐明外泌体生物发生与功能之间的关系，这将有助于转化应用的发展。
