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Proteomic analysis of Tn-bearing glycoproteins from different stages of melanoma cells reveals new biomarkers
Biochimie ( IF 3.3 ) Pub Date : 2018-05-24 , DOI: 10.1016/j.biochi.2018.05.010
Dorota Hoja-Łukowicz , Sabina Szwed , Piotr Laidler , Anna Lityńska

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.



中文翻译:

黑色素瘤细胞不同阶段的含Tn糖蛋白的蛋白质组学分析揭示了新的生物标志物

皮肤黑素瘤是皮肤癌中最具侵略性的一种形式,对常规疗法的反应较差。Tn抗原修饰的蛋白质在癌症中的出现与转移和预后不良有关。Tn决定簇已被公认为是强大的诊断和治疗靶标,也是开发抗肿瘤疫苗策略的对象。这项研究旨在鉴定携带Tn的蛋白质,并揭示其对皮肤黑色素瘤进展的影响。我们使用了基于凝集素的策略来纯化富含Tn抗原的细胞糖蛋白组,使用LC-MS / MS方法来鉴定分离的糖蛋白,并使用DAVID生物信息学工具对所鉴定的蛋白质进行分类。我们鉴定出146种不同的Tn糖蛋白,其中88%是新的。Tn-糖蛋白组通常富含与控制核糖体生物发生,CDR介导的mRNA稳定,细胞间粘附和细胞外囊泡形成有关的蛋白质。皮肤原发性和转移性黑色素瘤细胞的Tn修饰蛋白的差异表达模式分别支持非转移性和转移性细胞表型。据我们所知,这项研究是人类黑色素瘤细胞中含Tn的蛋白质的首次大规模蛋白质组学分析。鉴定出的Tn修饰蛋白与皮肤黑色素瘤的生物学和分子性质有关,可能是有价值的生物标志物和治疗靶标。皮肤原发性和转移性黑色素瘤细胞的Tn修饰蛋白的差异表达模式分别支持非转移性和转移性细胞表型。据我们所知,这项研究是人类黑色素瘤细胞中含Tn的蛋白质的首次大规模蛋白质组学分析。鉴定出的Tn修饰蛋白与皮肤黑色素瘤的生物学和分子性质有关,可能是有价值的生物标志物和治疗靶标。皮肤原发性和转移性黑色素瘤细胞的Tn修饰蛋白的差异表达模式分别支持非转移性和转移性细胞表型。据我们所知,这项研究是人类黑色素瘤细胞中含Tn的蛋白质的首次大规模蛋白质组学分析。鉴定出的Tn修饰蛋白与皮肤黑色素瘤的生物学和分子性质有关,可能是有价值的生物标志物和治疗靶标。

更新日期:2018-05-24
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