Apoptotic Extracellular Vesicles Ameliorate Multiple Myeloma by Restoring Fas-Mediated Apoptosis

作者：Juan Wang, Zeyuan Cao, Panpan Wang, Xiao Zhang, Jianxia Tang, Yifan He, Zhiqing Huang, Xueli Mao, Songtao Shi, Xiaoxing Kou · 发表于：ACS Nano · 年份：2021 · DOI：10.1021/acsnano.1c03517 · 被引用次数：139 · 研究领域：Extracellular vesicles in disease、Phagocytosis and Immune Regulation、MicroRNA in disease regulation

High Resolution Image Download MS PowerPoint Slide Apoptosis is critical for maintaining bodily homeostasis and produces a large number of apoptotic extracellular vesicles (apoEVs). Several types of cancer cells display reduced expression of Fas on the cell surface and are thus capable of escaping Fas ligand-induced apoptosis. However, it is unknown whether normal cell-derived apoEVs can regulate tumor growth. In this study, we show that apoEVs can induce multiple myeloma (MM) cell apoptosis and inhibit MM cell growth. Systemic infusion of mesenchymal stem cell (MSC)-derived apoEVs significantly prolongs the lifespan of MM mice. Mechanistically, apoEVs directly contact MM cells to facilitate Fas trafficking from the cytoplasm to the cell membrane by evoking Ca 2+ influx and elevation of cytosolic Ca 2+ . Subsequently, apoEVs use their Fas ligand to activate the Fas pathway in MM cells, leading to the initiation of apoptosis. This study identifies the role of apoEVs in inducing MM apoptosis and suggests a potential for apoEVs to treat MM.