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

• Published in: The Journal of biological chemistry 2022-06, Vol.298 (6), p.101950-101950, Article 101950
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: exosome (vesicle); extracellular vesicles; glycomics; glycosylation; integrins; lung cancers
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/j.jbc.2022.101950

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.