Thakur Abhimanyu, Johnson Amanda, Jacobs Emily, Zhang Kui, Chen Jonathan, Wei Zhubo, Lian Qizhou, Chen Huanhuan Joyce
The Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL 60637, USA.
The Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Cancers (Basel). 2022 Mar 27;14(7):1698. doi: 10.3390/cancers14071698.
Exosomes are crucial extracellular vesicles (EVs) with a diameter of approximately 30-200 nm. They are released by most cell types in their extracellular milieu and carry various biomolecules, including proteins and nucleic acids. Exosomes are increasingly studied in various diseases, including cancer, due to their role in local and distant cell-cell communication in which they can promote tumor growth, cancer progression, and metastasis. Interestingly, a tremendous number of exosomes is released by malignant cancer cells, and these are then taken up by autologous and heterologous recipient stromal cells such as immune cells, cancer stem cells, and endothelial cells. All these events demand an enormous amount of energy and require that exosomes remain stable while having the capacity to reach distant sites and cross physical barriers. Nevertheless, there is a dearth of research pertaining to the energy sources of exosomes, and questions remain about how they maintain their motility in the tumor microenvironment (TME) and beyond. Moreover, exosomes can produce adenosine triphosphate (ATP), an important energy molecule required by all cells, and mitochondria have been identified as one of the exosomal cargoes. These findings strengthen the prospect of exosomal communication via transfer of mitochondria and the bioenergetics of target recipient cells. In the TME, the accumulation of ATP and lactate may facilitate the entry of exosomes into cancer cells to promote metastasis, as well as help to target cancer cells at the tumor site. This review highlights how exosomes obtain sufficient energy to thrive in the TME and communicate with distant physiological destinations.
外泌体是至关重要的细胞外囊泡（EVs），直径约为30 - 200纳米。它们由大多数细胞类型释放到细胞外环境中，并携带各种生物分子，包括蛋白质和核酸。由于外泌体在局部和远距离细胞间通讯中发挥作用，可促进肿瘤生长、癌症进展和转移，因此在包括癌症在内的各种疾病中受到越来越多的研究。有趣的是，恶性癌细胞会释放大量外泌体，这些外泌体随后会被自体和异源受体基质细胞摄取，如免疫细胞、癌症干细胞和内皮细胞。所有这些过程都需要大量能量，并且要求外泌体在能够到达远处位点并穿越物理屏障的同时保持稳定。然而，关于外泌体的能量来源的研究却很匮乏，关于它们如何在肿瘤微环境（TME）及其他环境中维持运动性的问题仍然存在。此外，外泌体可以产生三磷酸腺苷（ATP），这是所有细胞都需要的重要能量分子，并且线粒体已被鉴定为外泌体的一种货物。这些发现增强了通过线粒体转移进行外泌体通讯以及靶受体细胞生物能量学的前景。在TME中，ATP和乳酸的积累可能有助于外泌体进入癌细胞以促进转移，同时也有助于在肿瘤部位靶向癌细胞。本综述重点介绍了外泌体如何获得足够的能量以在TME中茁壮成长并与远处的生理目的地进行通讯。
