Identification of distinct N-glycosylation patterns on extracellular vesicles from small-cell and non-small-cell lung cancer cells.

Identification of distinct N-glycosylation patterns on extracellular vesicles from small-cell and non-small-cell lung cancer cells.
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DOI:
10.1016/j.jbc.2022.101950
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发表时间:
2022-06
影响因子:
4.8
通讯作者:
Inoue, Hiromasa
Inoue, Hiromasa
中科院分区:
生物学2区
文献类型:
--
作者:
Kondo, Kiyotaka;Harada, Yoichiro;Nakano, Miyako;Suzuki, Takehiro;Fukushige, Tomoko;Hanzawa, Ken;Yagi, Hirokazu;Takagi, Koichi;Mizuno, Keiko;Miyamoto, Yasuhide;Taniguchi, Naoyuki;Kato, Koichi;Kanekura, Takuro;Dohmae, Naoshi;Machida, Kentaro;Maruyama, Ikuro;Inoue, Hiromasa

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作为一种潜在的癌症检测和诊断的生物标志物,肿瘤分泌组蛋白的天冬酰胺连接糖基化(n -糖基化)越来越受到关注。小的细胞外囊泡(sev)构成了癌症分泌组的很大一部分,但它们的n -糖基化状态是否反映了已知的癌症特征尚不清楚。在这里,我们研究了小细胞肺癌(SCLC)和非小细胞肺癌(NSCLC)细胞释放的sev的n -糖基化。我们发现sclc - sev的n -聚糖的特征是存在与脑n -聚糖相同的结构单元,而nsclc - sev主要是典型的肺型n -聚糖,具有nsclc相关的核心聚焦。此外,凝集素辅助的sclc - sev和nsclc - sev的n-糖蛋白组学结果显示,整合素αV在两种癌细胞类型的sev中均有表达,而上皮特异性整合素α6β4异源二聚体在nsclc - sev中有选择性表达。重要的是,来自nsclc - sev的免疫纯化整合素α6的n糖组学鉴定出该整合素亚基上的nsclc型n聚糖。因此,我们得出结论,肺癌sev中的蛋白n -糖基化可能潜在地反映了肺癌的组织学。
Asparagine-linked glycosylation (N-glycosylation) of proteins in the cancer secretome has been gaining increasing attention as a potential biomarker for cancer detection and diagnosis. Small extracellular vesicles (sEVs) constitute a large part of the cancer secretome, yet little is known about whether their N-glycosylation status reflects known cancer characteristics. Here, we investigated the N-glycosylation of sEVs released from small-cell lung carcinoma (SCLC) and non–small-cell lung carcinoma (NSCLC) cells. We found that the N-glycans of SCLC-sEVs were characterized by the presence of structural units also found in the brain N-glycome, while NSCLC-sEVs were dominated by typical lung-type N-glycans with NSCLC-associated core fucosylation. In addition, lectin-assisted N-glycoproteomics of SCLC-sEVs and NSCLC-sEVs revealed that integrin αV was commonly expressed in sEVs of both cancer cell types, while the epithelium-specific integrin α6β4 heterodimer was selectively expressed in NSCLC-sEVs. Importantly, N-glycomics of the immunopurified integrin α6 from NSCLC-sEVs identified NSCLC-type N-glycans on this integrin subunit. Thus, we conclude that protein N-glycosylation in lung cancer sEVs may potentially reflect the histology of lung cancers.
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