{Reference Type}: Journal Article
{Title}: Secreted phospholipase A2 modifies extracellular vesicles and accelerates B cell lymphoma.
{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;
{Journal}: Cell Metab
{Volume}: 34
{Issue}: 4
{Year}: 04 2022 5
{Factor}: 31.373
{DOI}: 10.1016/j.cmet.2022.02.011
{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.