RRC ID 72824
Author Kudo K, Miki Y, Carreras J, Nakayama S, Nakamoto Y, Ito M, Nagashima E, Yamamoto K, Higuchi H, Morita SY, Inoue A, Aoki J, Ando K, Nakamura N, Murakami M, Kotani A.
Title Secreted phospholipase A2 modifies extracellular vesicles and accelerates B cell lymphoma.
Journal Cell Metab
Abstract 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.
Volume 34(4)
Pages 615-633.e8
Published 2022-4-5
DOI 10.1016/j.cmet.2022.02.011
PII S1550-4131(22)00083-3
PMID 35294862
MeSH Animals Epstein-Barr Virus Infections* Extracellular Vesicles* Herpesvirus 4, Human Humans Lymphoma* Lymphoma, B-Cell* Mice Phospholipases A2, Secretory*
IF 21.567
Resource
Cord blood stem cells for research RCB1437 RCB1438 RCB1487