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Proteomic analysis of Tn-bearing glycoproteins from different stages of melanoma cells reveals new biomarkers.
Biochimie 2018 August
Cutaneous melanoma, the most aggressive form of skin cancer, responds poorly to conventional therapy. The appearance of Tn antigen-modified proteins in cancer is correlated with metastasis and poor prognoses. The Tn determinant has been recognized as a powerful diagnostic and therapeutic target, and as an object for the development of anti-tumor vaccine strategies. This study was designed to identify Tn-carrying proteins and reveal their influence on cutaneous melanoma progression. We used a lectin-based strategy to purify Tn antigen-enriched cellular glycoproteome, the LC-MS/MS method to identify isolated glycoproteins, and the DAVID bioinformatics tool to classify the identified proteins. We identified 146 different Tn-bearing glycoproteins, 88% of which are new. The Tn-glycoproteome was generally enriched in proteins involved in the control of ribosome biogenesis, CDR-mediated mRNA stabilization, cell-cell adhesion and extracellular vesicle formation. The differential expression patterns of Tn-modified proteins for cutaneous primary and metastatic melanoma cells supported nonmetastatic and metastatic cell phenotypes, respectively. To our knowledge, this study is the first large-scale proteomic analysis of Tn-bearing proteins in human melanoma cells. The identified Tn-modified proteins are related to the biological and molecular nature of cutaneous melanoma and may be valuable biomarkers and therapeutic targets.
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