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Updated: Sep 30, 2025

Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
Secreted phospholipase A2 modifies extracellular vesicles and accelerates B cell lymphoma
Kai Kudo1, Yoshimi Miki2, Joaquim Carreras3
1Department of Innovative Medical Science, Tokai University School of Medicine, Isehara, Japan; Division of Hematological Malignancy, Institute of Medical Sciences, Tokai University, Isehara, Japan.
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.
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