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Proteomic Analysis of Extracellular Vesicles Derived from MDA-MB-231 Cells in Microgravity
The Protein Journal ( IF 3 ) Pub Date : 2021-01-02 , DOI: 10.1007/s10930-020-09949-2
Yundi Chen 1 , Fei Xue 1 , Andrea Russo 1 , Yuan Wan 1, 2
Affiliation  

Patients with triple-negative breast cancer (TNBC) have a relatively poor prognosis and cannot benefit from endocrine and/or targeted therapy. Considerable effort has been devoted toward the elucidation of the molecular mechanisms and potential diagnostic/therapeutic targets. However, it is inefficient and often ineffective to study the biological nuances of TNBC in large-scale clinical trials. In contrast, the investigation of the association between molecular alterations induced through controlled variables and relevant physiochemical characteristics of TNBC cells in laboratory settings is simple, definite, and efficient in exploring the molecular mechanisms. In this study, microgravity was selected as the sole variable of study as it can inhibit cancer cell viability, proliferation, metastasis, and chemoresistance. Identifying the key molecules that shift cancer cells toward a less aggressive phenotype may facilitate future TNBC studies. We focused on extracellular vesicles (EV) derived from TNBC MDA-MB-231 cells in microgravity, which mediate intercellular communication by transporting signaling molecules between cells. Our results show that in comparison with cells in full gravity, EV release rate decreased in microgravity while average EV size increased. In addition, we found EVs may be superior to cells in analyzing differentially expressed proteins, especially those that are down-regulated ones and usually unidentified or neglected in analysis of intact cellular contents. Proteomic analysis of both EVs and cells further revealed a significant correlation with GTPases and proliferation of MDA-MB-231 cells in microgravity. Altogether, our findings would further inspire in-depth correlative cancer biological studies and subsequent clinical research.



中文翻译:

微重力下 MDA-MB-231 细胞衍生的细胞外囊泡的蛋白质组学分析

三阴性乳腺癌(TNBC)患者预后相对较差,不能从内分泌和/或靶向治疗中获益。相当多的努力致力于阐明分子机制和潜在的诊断/治疗目标。然而,在大规模临床试验中研究 TNBC 的生物学细微差别是低效的,而且往往是无效的。相比之下,在实验室环境中通过受控变量诱导的分子改变与 TNBC 细胞的相关理化特征之间的关联的研究在探索分子机制方面简单、明确且有效。在这项研究中,微重力被选为研究的唯一变量,因为它可以抑制癌细胞的活力、增殖、转移和化学抗性。确定将癌细胞转变为侵袭性较低的表型的关键分子可能有助于未来的 TNBC 研究。我们专注于微重力下源自 TNBC MDA-MB-231 细胞的细胞外囊泡 (EV),其通过在细胞之间传输信号分子来介导细胞间通讯。我们的结果表明,与全重力下的细胞相比,微重力下的 EV 释放率降低,而平均 EV 尺寸增加。此外,我们发现 EV 在分析差异表达的蛋白质方面可能优于细胞,尤其是那些下调的蛋白质,并且在分析完整细胞内容时通常未被识别或被忽视。EVs 和细胞的蛋白质组学分析进一步揭示了与 GTP 酶和 MDA-MB-231 细胞在微重力下的增殖的显着相关性。共,

更新日期:2021-01-02
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