Tasmanian devils are threatened with extinction by Devil Facial Tumor Disease (DFTD), which consists of two genetically independent transmissible cancers (DFT1 and DFT2). Both cancers typically cause death due to metastases. However, the mechanisms underpinning DFTD metastasis are not well understood. The nano-sized, membrane-enclosed extracellular vesicles (EVs) released by cancer cells have been implicated in metastasis, thus EVs may yield insights into DFTD metastasis. Here, we characterized EVs derived from cultured DFT1, DFT2, and devil fibroblast cells. The proteome of EVs was determined using data-independent acquisition mass spectrometry and an in-house spectral library of >1,500 proteins. Relative to EVs from fibroblast cells, EVs from both DFT1 and DFT2 cell lines expressed higher levels of proteins associated with cell adhesion and focal adhesion functions. Furthermore, hallmark proteins of epithelial-mesenchymal transition, which are associated with increased metastatic features in some cancers, were enriched in DFT2 EVs relative to DFT1 EVs, suggesting differential aggressiveness between the cancers and a target for novel differential diagnosis biomarkers. This first EV-based investigation of DFTD increases our understanding of the cancers' EVs and their possible involvement in the metastatic process. As EVs are found in body fluids, these results offer potential for non-invasive biomarkers for DFTD.

中文翻译：

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塔斯马尼亚恶魔面部肿瘤衍生的细胞外囊泡揭示了与转移相关的间充质转移标志物和粘附分子。

塔斯马尼亚恶魔正面临魔鬼面部肿瘤病（DFTD）的灭绝威胁，该病由两种遗传上独立的可传播癌症（DFT1和DFT2）组成。两种癌症通常都会因转移而导致死亡。然而，尚不清楚DFDF转移的基础机制。癌细胞释放的纳米级，膜封闭的细胞外囊泡（EVs）与转移有关，因此，EVs可能有助于深入了解DFTD转移。在这里，我们表征了从培养的DFT1，DFT2和魔鬼成纤维细胞衍生的EV。EV的蛋白质组使用独立于数据的采集质谱法和超过1,500种蛋白质的内部光谱库确定。相对于成纤维细胞的电动汽车，DFT1和DFT2细胞系的EV均表达较高水平的蛋白质，这些蛋白质与细胞粘附和黏附粘附功能有关。此外，相对于DFT1 EV，DFT2 EV中富含上皮-间质转化的标志性蛋白（与某些癌症的转移特征增加相关），表明癌症之间的差异攻击性与新型差异诊断生物标志物的靶标有关。对DFTD进行的首次基于电动的研究，使我们对癌症的电动汽车及其可能参与转移过程的理解更加深入。由于在体液中发现了电动汽车，这些结果为DFTD的非侵入性生物标记物提供了潜力。相对于DFT1电动汽车，DFT2电动汽车富含DFT2电动汽车，表明癌症与新型鉴别诊断生物标志物的靶标之间具有不同的攻击性。对DFTD进行的首次基于电动的研究，使我们对癌症的电动汽车及其可能参与转移过程的理解更加深入。由于在体液中发现了电动汽车，这些结果为DFTD的非侵入性生物标记物提供了潜力。相对于DFT1电动汽车，DFT2电动汽车富含DFT2电动汽车，表明癌症与新型鉴别诊断生物标志物的靶标之间具有不同的攻击性。对DFTD进行的首次基于电动的研究，使我们对癌症的电动汽车及其可能参与转移过程的理解更加深入。由于在体液中发现了电动汽车，这些结果为DFTD的非侵入性生物标记物提供了潜力。