小柯机器人

日本东海大学Ai Kotani、东京大学Makoto Murakami等研究人员合作发现，分泌型磷脂酶A2修饰细胞外囊泡并加速B细胞淋巴瘤。这一研究成果于2022年3月15日在线发表在国际学术期刊《细胞—代谢》上。

研究人员发现，淋巴瘤来源的细胞外囊泡（EV）的促肿瘤作用是通过分泌的磷脂酶A2（sPLA2）驱动的脂质代谢而增强的。在Epstein-Barr病毒（EBV）淋巴瘤的巨噬细胞中诱导的X组sPLA2对EV磷脂的水解，增加了脂肪酸、溶血磷脂及其代谢产物的产生。sPLA2处理过的EV更小、更自聚，显示出更好的吸收能力，并增加了肿瘤相关巨噬细胞的细胞因子表达和脂质介质信号。内源性sPLA2的药物抑制阻碍了EBV感染的人源化小鼠的淋巴瘤生长，而用sPLA2修饰的EV治疗则逆转了这种表型。此外，sPLA2在人类大B细胞淋巴瘤中的表达与患者的生存率成反比。

总的来说，sPLA2介导的EV修饰促进了肿瘤的发展，突出了EV作为sPLA2胞外水解平台的非经典机制作用。

据悉，包括外泌体在内的EV通过转移蛋白质和microRNA货物充当细胞间的交流者，但EV脂质的作用仍不清楚。

附：英文原文

Title: Secreted phospholipase A2 modifies extracellular vesicles and accelerates B cell lymphoma

Author: Kai Kudo, Yoshimi Miki, Joaquim Carreras, Shunya Nakayama, Yasushi Nakamoto, Masatoshi Ito, Etsuko Nagashima, Kei Yamamoto, Hiroshi Higuchi, Shin-ya Morita, Asuka Inoue, Junken Aoki, Kiyoshi Ando, Naoya Nakamura, Makoto Murakami, Ai Kotani

Issue&Volume: 2022-03-15

Abstract: Extracellular vesicles (EVs) including exosomes act as intercellular communicatorsby 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 augmentedvia 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, increasedthe production of fatty acids, lysophospholipids, and their metabolites. sPLA2-treated EVs were smaller and self-aggregated, showed better uptake, and increasedcytokine 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-canonicalmechanistic action of EVs as an extracellular hydrolytic platform of sPLA2.

DOI: 10.1016/j.cmet.2022.02.011

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00083-3

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