Proteomic Characterization of Epithelial-Like Extracellular Vesicles in Advanced Endometrial Cancer
Proteomic Characterization of Epithelial-Like Extracellular Vesicles in Advanced Endometrial Cancer
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DOI：
10.1021/acs.jproteome.8b00750
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发表时间：
2019-03-01
影响因子：
4.4
通讯作者：
Abal, Miguel
中科院分区：
文献类型：
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作者：
Mariscal, Javier;Fernandez-Puente, Patricia;Abal, Miguel
子宫内膜癌是最常见的妇科肿瘤。大约20%的EC患者的肿瘤播散以原发癌的上皮-间质转化（EMT）为特征，并伴有肌层浸润。在远处，循环肿瘤细胞（CTCs）与微环境的相互作用对于转移定植至关重要，细胞外囊泡（ev）也参与其中。我们综合了这些原发和继发部位，研究肿瘤ev对EC中ctc转移效率的影响。循环中的肿瘤EVs复制原发癌中主要的上皮表型，而ctc则以EMT表型为特征。我们在Hec1A子宫内膜细胞系中模拟了这种emt相关的临床场景，并通过SILAC蛋白质组分析表征了循环中的上皮样EVs。细胞-细胞和细胞-基质相互作用和结合的蛋白的鉴定，以及体外证据表明，CTC与内皮细胞的粘附改善，表明上皮样ev在转移部位的CTC归巢中起作用。通过靶向蛋白质组学（多反应监测）发现，黏附蛋白LGALS3BP在一组复发风险高的EC患者的循环EVs中显著富集，突出了其在EC液体活检中的潜力。
Endometrial cancer (EC) is the most frequent gynecological cancer. Tumor dissemination affecting similar to 20% of EC patients is characterized at the primary carcinoma by epithelial-to-mesenchymal transition (EMT) associated with myometrial infiltration. At distant sites, the interaction of circulating tumor cells (CTCs) with the microenvironment is crucial for metastatic colonization, with a participation of the extracellular vesicles (EVs). We comprehensively approached these primary and secondary sites to study the impact of tumor EVs on the metastatic efficiency of CTCs in EC. Tumor EVs in circulation reproduce the epithelial phenotype predominant in the primary carcinoma, whereas CTCs are characterized by an EMT phenotype. We modeled this EMT-related clinical scenario in the Hec1A endometrial cell line and characterized the epithelial-like EVs in circulation by SILAC proteome analysis. The identification of proteins involved in cell-cell and cell-matrix interaction and binding, together with in vitro evidence of an improved adhesion of CTC to a endothelium, suggests a contribution of the epithelial-like EVs in the homing of CTCs at metastatic sites. adhesion protein LGALS3BP was found to be significantly enriched in circulating EVs from a cohort of EC patients with a high risk of recurrence by targeted proteomics (multiple reaction monitoring), highlighting its potential in liquid biopsy in EC.