Surface and whole-cell lysate glycomic profiling reveals N-glycosylation features associated with metastatic potential in non-small cell lung cancer.

Authors

Seojeong Lee, Haeun Byeon, Chi Soo Park, Chulmin Moon, Daeun Eom, Siwon Kim, Jihyeon Lee, Yejin Park, Taeyong An, Ha Hyung Kim

Published in

Journal of proteomics. Pages 105741. Oct 13, 2026. Epub Oct 13, 2026.

Abstract

Cell-surface N-glycans mediate interactions with the tumor microenvironment, whereas whole-cell lysate N-glycans reflect glycoprotein biosynthesis and maturation along the endoplasmic reticulum-Golgi pathway. Although glycomic analyses have revealed cancer-associated N-glycan alterations, the relationship between surface and lysate N-glycomes and metastasis-associated N-glycosylation in non-small cell lung cancer (NSCLC) remains poorly understood. In this study, surface and lysate N-glycomes of the NSCLC cell lines A549 (lower metastatic potential) and H1299 (higher metastatic potential) were profiled using liquid chromatography-electrospray ionization-high-energy collision dissociation tandem mass spectrometry (LC-ESI-HCD-MS/MS), enabling structural characterization with high mass accuracies below 2.0 ppm and relative quantification of individual N-glycans. A total of 59 surface and 54 lysate N-glycans were identified in A549, whereas 70 surface and 71 lysate N-glycans were identified in H1299. Surface N-glycomes were enriched in mature complex-type glycans (55.9% in A549 and 60.0% in H1299), whereas lysates were enriched in high-mannose glycans (49.3% and 40.7%), reflecting distinct stages of glycoprotein maturation. Across surface and lysate N-glycomes, N-acetyllactosamine, a precursor of Lewis x and sialyl Lewis x, was similarly distributed in A549 and H1299; however, H1299 cells displayed consistent enrichment of fucosylation (41.0% in surface and 52.3% in lysate), tri-/tetra-antennary branching (7.3% and 17.8%), Lewis x (4.7% and 4.2%) and sialyl Lewis x (0.1% and 0.1%), representing N-glycosylation features associated with the higher metastatic of H1299 cells. This study provides the first integrated glycomic characterization of metastasis-associated N-glycosylation features across surface and lysate and quantitatively characterizes their association with the metastatic phenotype.

PMID:
42869108
Bibliographic data and abstract were imported from PubMed on 14 Oct 2026.

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