Structural and Quantitative Surface N-Glycomic Profiling of Cisplatin-Treated Melanoma Cells with Distinct Metastatic Potential

Abstract

Melanoma is a highly aggressive skin cancer with strong metastatic potential and frequent chemoresistance. Aberrant N-glycosylation plays a critical role in tumor progression and drug resistance; however, cisplatin-induced alterations in melanoma surface N-glycans remain poorly understood. Thus, this study aimed to perform comprehensive structural and quantitative profiling of surface N-glycans in G-361 (low metastatic potential), A375P (moderate), and SK-MEL-28 (high) melanoma cells following cisplatin treatment using LC–MS/MS. A total of 25, 39, and 28 surface N-glycans were identified in untreated G-361, A375P, and SK-MEL-28 cells, respectively, whereas 40, 37, and 40 N-glycans were detected after cisplatin treatment. Absolute quantification revealed a marked increase in total N-glycan abundance in G-361 (3.2 to 8.4 pmol) and A375P (5.7 to 10.9 pmol), whereas SK-MEL-28 maintained homeostasis (3.9 to 4.0 pmol). Surface N-glycans were predominantly high-mannose and complex-type glycans with extensive sialylation and fucosylation. Cisplatin induced distinct cell line-specific remodeling: G-361 accumulated high-mannose glycans with reduced Neu5Gc-containing sialylation; A375P showed increased glycan branching and Neu5Ac-containing sialylation; and SK-MEL-28 maintained a stable glycan distribution but exhibited increased Neu5Gc-containing sialylation. These results demonstrate adaptive N-glycosylation responses to cisplatin in melanoma cells with distinct metastatic potentials and provide a glycomic framework for understanding cisplatin-associated glycan alterations.