缺氧是实体瘤的一个常见特征，会激活癌细胞的适应机制，从而诱导治疗抵抗，并对细胞代谢产生深远影响。因此，缺氧是癌症进展的重要因素，并与不良预后相关。肿瘤微环境内细胞的代谢改变通过抑制免疫反应和诱导血管生成等方式支持肿瘤生长。最近，细胞外囊泡（EV）已成为支持癌症进展的细胞间通讯的重要介质。之前，我们证明了缺氧癌细胞衍生的 EV 的促血管生成特性。在这项研究中，我们研究了（缺氧）癌细胞衍生的 EV 如何介导其作用。我们证明，癌症衍生的 EV 通过增加 mTOR 和 AMPKα 的激活来调节受体细胞中的细胞代谢和蛋白质合成。通过代谢示踪实验，我们证明 EV 刺激内皮细胞中的葡萄糖摄取，以促进氨基酸合成，并刺激氨基酸摄取以增加蛋白质合成。尽管货物发生了变化，我们表明癌症衍生的 EV 对受体细胞的影响主要取决于产生 EV 的癌细胞类型，而不是其氧合状态。© 2024 作者。 《Journal of Extracellular Vesicles》由 Wiley periodicals LLC 代表国际细胞外囊泡学会出版。

Hypoxia is a common feature of solid tumours and activates adaptation mechanisms in cancer cells that induce therapy resistance and has profound effects on cellular metabolism. As such, hypoxia is an important contributor to cancer progression and is associated with a poor prognosis. Metabolic alterations in cells within the tumour microenvironment support tumour growth via, amongst others, the suppression of immune reactions and the induction of angiogenesis. Recently, extracellular vesicles (EV) have emerged as important mediators of intercellular communication in support of cancer progression. Previously, we demonstrated the pro-angiogenic properties of hypoxic cancer cell derived EV. In this study, we investigate how (hypoxic) cancer cell derived EV mediate their effects. We demonstrate that cancer derived EV regulate cellular metabolism and protein synthesis in acceptor cells through increased activation of mTOR and AMPKα. Using metabolic tracer experiments, we demonstrate that EV stimulate glucose uptake in endothelial cells to fuel amino acid synthesis and stimulate amino acid uptake to increase protein synthesis. Despite alterations in cargo, we show that the effect of cancer derived EV on recipient cells is primarily determined by the EV producing cancer cell type rather than its oxygenation status.© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.