PDF(Pubmed)
Abstract：
Ewing sarcoma (EWS) is an aggressive pediatric bone tumor characterized by unmet clinical needs and an incompletely understood epigenetic heterogeneity. Here, we considered CD99, a major surface molecule hallmark of EWS malignancy. Fluctuations in CD99 expression strongly impair cell dissemination, differentiation, and death. CD99 is also loaded within extracellular vesicles (EVs), and the delivery of CD99-positive or CD99-negative EVs dynamically exerts oncogenic or oncosuppressive functions to recipient cells, respectively. We undertook mass spectrometry and functional annotation analysis to investigate the consequences of CD99 silencing on the proteomic landscape of EWS cells and related EVs. Our data demonstrate that (i) the decrease in CD99 leads to major changes in the proteomic profile of EWS cells and EVs; (ii) intracellular and extracellular compartments display two distinct signatures of differentially expressed proteins; (iii) proteomic changes converge to the modulation of cell migration and immune-modulation biological processes; and (iv) CD99-silenced cells and related EVs are characterized by a migration-suppressive, pro-immunostimulatory proteomic profile. Overall, our data provide a novel source of CD99-associated protein biomarkers to be considered for further validation as mediators of EWS malignancy and as EWS disease liquid biopsy markers.
摘要：
尤文肉瘤（EWS）是一种侵袭性小儿骨肿瘤，其特征是临床需求未得到满足，表观遗传异质性尚未完全理解。这里,我们认为CD99是EWS恶性肿瘤的主要表面分子标志。CD99表达的波动强烈损害细胞播散，分化,和死亡。CD99也加载在细胞外囊泡（EV）内，并且CD99阳性或CD99阴性EV的递送动态地对受体细胞发挥致癌或抑癌功能，分别。我们进行了质谱和功能注释分析，以研究CD99沉默对EWS细胞和相关EV的蛋白质组景观的影响。我们的数据表明，（i）CD99的减少导致EWS细胞和EV的蛋白质组学谱发生重大变化；（ii）细胞内和细胞外区室显示出差异表达蛋白的两个不同特征；（iii）蛋白质组学变化收敛于细胞迁移和免疫调节生物学过程的调节；（iv）CD99沉默的细胞和相关的EV的特征是迁移抑制，前免疫刺激蛋白质组学图谱。总的来说,我们的数据提供了CD99相关蛋白生物标志物的新来源,可考虑作为EWS恶性肿瘤的介质和EWS疾病液体活检标志物进行进一步验证.
