%0 Journal Article
%T Secreted phospholipase A2 modifies extracellular vesicles and accelerates B cell lymphoma.
%A Kudo K
%A Miki Y
%A Carreras J
%A Nakayama S
%A Nakamoto Y
%A Ito M
%A Nagashima E
%A Yamamoto K
%A Higuchi H
%A Morita SY
%A Inoue A
%A Aoki J
%A Ando K
%A Nakamura N
%A Murakami M
%A Kotani A
%J Cell Metab
%V 34
%N 4
%D 04 2022 5
%M 35294862
%F 31.373
%R 10.1016/j.cmet.2022.02.011
%X 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.