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甲状腺癌细胞和正常甲状腺细胞来源的外泌体的比较蛋白质组学分析揭示了多种在癌症中具有功能意义的蛋白质。

Comparative Proteomic Profiling of Ectosomes Derived from Thyroid Carcinoma and Normal Thyroid Cells Uncovers Multiple Proteins with Functional Implications in Cancer.

机构信息

Department of Glycoconjugate Biochemistry, Faculty of Biology, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, 30-387 Krakow, Poland.

Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, 30-387 Krakow, Poland.

出版信息

Cells. 2022 Mar 31;11(7):1184. doi: 10.3390/cells11071184.

DOI:10.3390/cells11071184
PMID:35406748
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8997476/
Abstract

Proteins carried by tumor-derived ectosomes play an important role in cancer progression, and are considered promising diagnostic markers. In the present study, a shotgun nanoLC-MS/MS proteomic approach was applied to profile and compare the protein content of ectosomes released in vitro by normal human thyroid follicular epithelial Nthy-ori 3-1 cells and human anaplastic thyroid carcinoma (TC) 8305C cells. Additionally, the pro-migratory and pro-proliferative effects of Nthy-ori 3-1- and 8305C-derived ectosomes exerted on the recipient cells were assessed in wound closure and Alamar Blue assays. A total of 919 proteins were identified in all replicates of 8305C-derived ectosomes, while Nthy-ori 3-1-derived ectosomes contained a significantly lower number of 420 identified proteins. Qualitative analysis revealed 568 proteins present uniquely in 8305C-derived ectosomes, suggesting their applicability in TC diagnosis and management. In addition, 8305C-derived ectosomes were able to increase the proliferation and motility rates of the recipient cells, likely due to the ectosomal transfer of the identified cancer-promoting molecules. Our description of ectosome protein content and its related functions provides the first insight into the role of ectosomes in TC development and progression. The results also indicate the applicability of some of these ectosomal proteins for further investigation regarding their potential as circulating TC biomarkers.

摘要

肿瘤衍生的外泌体所携带的蛋白质在癌症进展中发挥着重要作用，被认为是很有前途的诊断标志物。在本研究中，采用鸟枪法 nanoLC-MS/MS 蛋白质组学方法对正常人类甲状腺滤泡上皮 Nthy-ori 3-1 细胞和人间变性甲状腺癌（TC）8305C 细胞体外释放的外泌体的蛋白质含量进行了分析和比较。此外，还通过划痕闭合和 Alamar Blue 测定评估了 Nthy-ori 3-1-和 8305C 衍生的外泌体对受体细胞的促迁移和促增殖作用。在所有 8305C 衍生的外泌体重复实验中鉴定到了 919 种蛋白质，而 Nthy-ori 3-1 衍生的外泌体中仅鉴定到了 420 种蛋白质。定性分析显示，568 种蛋白质仅存在于 8305C 衍生的外泌体中，这表明它们可能适用于 TC 的诊断和管理。此外，8305C 衍生的外泌体能够增加受体细胞的增殖和迁移率，这可能是由于鉴定出的促进癌症的分子从外泌体转移。我们对外泌体蛋白质含量及其相关功能的描述首次揭示了外泌体在 TC 发生和发展中的作用。研究结果还表明，其中一些外泌体蛋白具有作为循环 TC 生物标志物的进一步研究的应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/87c979584d99/cells-11-01184-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/8882e22fb686/cells-11-01184-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/7f3d72df2b75/cells-11-01184-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/b84b8a0ddba0/cells-11-01184-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/47563d20706e/cells-11-01184-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/9e7db65d2664/cells-11-01184-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/66b1d5469390/cells-11-01184-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/cad9954bdb9e/cells-11-01184-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/77cd8a88372b/cells-11-01184-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/e044c8b18dd4/cells-11-01184-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/87c979584d99/cells-11-01184-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/8882e22fb686/cells-11-01184-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/7f3d72df2b75/cells-11-01184-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/b84b8a0ddba0/cells-11-01184-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/47563d20706e/cells-11-01184-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/9e7db65d2664/cells-11-01184-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/66b1d5469390/cells-11-01184-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/cad9954bdb9e/cells-11-01184-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/77cd8a88372b/cells-11-01184-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/e044c8b18dd4/cells-11-01184-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0844/8997476/87c979584d99/cells-11-01184-g010.jpg

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