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 Ca²⁺ influx and elevation of cytosolic Ca²⁺. 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.

中文翻译：

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凋亡细胞外囊泡通过恢复 Fas 介导的细胞凋亡改善多发性骨髓瘤

细胞凋亡对于维持身体稳态至关重要，并产生大量凋亡细胞外囊泡 (apoEVs)。几种类型的癌细胞显示出细胞表面 Fas 表达减少，因此能够逃避 Fas 配体诱导的细胞凋亡。然而，尚不清楚正常细胞来源的 apoEVs 是否可以调节肿瘤生长。在这项研究中，我们表明 apoEVs 可以诱导多发性骨髓瘤 (MM) 细胞凋亡并抑制 MM 细胞生长。系统性输注间充质干细胞 (MSC) 衍生的 apoEVs 可显着延长 MM 小鼠的寿命。从机制上讲，apoEVs 直接接触 MM 细胞，通过引起 Ca ²⁺流入和细胞溶质 Ca ²⁺升高来促进 Fas 从细胞质运输到细胞膜. 随后，apoEVs 使用它们的 Fas 配体激活 MM 细胞中的 Fas 通路，导致细胞凋亡的开始。该研究确定了 apoEVs 在诱导 MM 细胞凋亡中的作用，并表明 apoEVs 治疗 MM 的潜力。