Secreted phospholipase A<sub>2</sub> modifies extracellular vesicles and accelerates B cell lymphoma.
basic_science · Level V
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- Record sourced from PubMed, PMID 35294862.
- Also identified by DOI 10.1016/j.cmet.2022.02.011.
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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 A<sub>2</sub> (sPLA<sub>2</sub>)-driven lipid metabolism. Hydrolysis of EV phospholipids by group X sPLA<sub>2</sub>, which was induced in macrophages of Epstein-Barr virus (EBV) lymphoma, increased the production of fatty acids, lysophospholipids, and their metabolites. sPLA<sub>2</sub>-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 sPLA<sub>2</sub> suppressed lymphoma growth in EBV-infected humanized mice, while treatment with sPLA<sub>2</sub>-modified EVs reversed this phenotype. Furthermore, sPLA<sub>2</sub> expression in human large B cell lymphomas inversely correlated with patient survival. Overall, the sPLA<sub>2</sub>-mediated EV modification promotes tumor development, highlighting a non-canonical mechanistic action of EVs as an extracellular hydrolytic platform of sPLA<sub>2</sub>.
Medical subject headings
- Epstein-Barr Virus Infections
- Extracellular Vesicles
- Lymphoma
- Lymphoma, B-Cell
- Phospholipases A2, Secretory