微泡
磷脂酶A2
细胞外
细胞生物学
细胞内
生物
B细胞淋巴瘤
淋巴瘤
外体
脂质代谢
脂质信号
磷脂酶D
酶
化学
生物化学
小RNA
信号转导
免疫学
基因
作者
Kai Kudo,Yoshimi Miki,Joaquim Carreras,Shunya Nakayama,Yasushi Nakamoto,Masatoshi Ito,Etsuko Nagashima,Kei Yamamoto,Hiroshi Higuchi,Shin‐ya Morita,Asuka Inoue,Junken Aoki,Kiyoshi Ando,Naoya Nakamura,Makoto Murakami,Ai Kotani
出处
期刊:Cell Metabolism
[Elsevier]
日期:2022-03-15
卷期号:34 (4): 615-633.e8
被引量:46
标识
DOI:10.1016/j.cmet.2022.02.011
摘要
Extracellular vesicles (EVs) including exosomes act as intercellular communicators by transferring protein and microRNA cargoes, yet the role of EV lipids remains unclear. Here, we show that the pro-tumorigenic action of lymphoma-derived EVs is augmented via secreted phospholipase A2 (sPLA2)-driven lipid metabolism. Hydrolysis of EV phospholipids by group X sPLA2, which was induced in macrophages of Epstein-Barr virus (EBV) lymphoma, increased the production of fatty acids, lysophospholipids, and their metabolites. sPLA2-treated EVs were smaller and self-aggregated, showed better uptake, and increased cytokine expression and lipid mediator signaling in tumor-associated macrophages. Pharmacological inhibition of endogenous sPLA2 suppressed lymphoma growth in EBV-infected humanized mice, while treatment with sPLA2-modified EVs reversed this phenotype. Furthermore, sPLA2 expression in human large B cell lymphomas inversely correlated with patient survival. Overall, the sPLA2-mediated EV modification promotes tumor development, highlighting a non-canonical mechanistic action of EVs as an extracellular hydrolytic platform of sPLA2.
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