乳房脂肪组织是肥胖与乳腺癌联系的重要贡献者。细胞外囊泡 (EV) 是含有选择性货物（例如 miRNA）的纳米级颗粒，可在局部发挥作用或循环到远处以调节靶细胞功能。在这里，我们发现用从超重或肥胖女性的乳腺脂肪组织中获得的 EV（O-EV）对乳腺癌细胞进行长期培养会导致增殖增加。对 O-EV 培养的细胞进行 RNA 测序分析表明，参与氧化磷酸化的基因表达增加，例如 ATP 合酶和 NADH：泛醌氧化还原酶。 O-EVs 增加肿瘤细胞中呼吸复合体蛋白的表达、线粒体密度和线粒体呼吸。线粒体复合物 I 抑制剂二甲双胍可逆转 O-EV 诱导的细胞增殖。与瘦女性的 EV 相比，O-EV 中富含一些促进线粒体呼吸和增殖的 miRNA（miR-155-5p、miR-10a-3p 和 miR-30a-3p）。 O-EV 诱导的增殖和线粒体活性与 Akt/mTOR/P70S6K 通路的刺激相关，并且在 P70S6K 沉默后逆转。这项研究揭示了肥胖乳腺癌与人类乳腺脂肪组织衍生的 EV 之间的联系的一个新方面，导致乳腺癌细胞的代谢重编程。© 2023 作者。

Breast adipose tissue is an important contributor to the obesity-breast cancer link. Extracellular vesicles (EVs) are nanosized particles containing selective cargo, such as miRNAs, that act locally or circulate to distant sites to modulate target cell functions. Here, we find that long-term education of breast cancer cells with EVs obtained from breast adipose tissue of women who are overweight or obese (O-EVs) results in increased proliferation. RNA-seq analysis of O-EV-educated cells demonstrates increased expression of genes involved in oxidative phosphorylation, such as ATP synthase and NADH: ubiquinone oxidoreductase. O-EVs increase respiratory complex protein expression, mitochondrial density, and mitochondrial respiration in tumor cells. The mitochondrial complex I inhibitor metformin reverses O-EV-induced cell proliferation. Several miRNAs-miR-155-5p, miR-10a-3p, and miR-30a-3p-which promote mitochondrial respiration and proliferation, are enriched in O-EVs relative to EVs from lean women. O-EV-induced proliferation and mitochondrial activity are associated with stimulation of the Akt/mTOR/P70S6K pathway, and are reversed upon silencing of P70S6K. This study reveals a new facet of the obesity-breast cancer link with human breast adipose tissue-derived EVs causing metabolic reprogramming of breast cancer cells.© 2023 The Authors.