Proteomic Analysis of Extracellular Vesicles Derived from MDA-MB-231 Cells in Microgravity.
Proteomic Analysis of Extracellular Vesicles Derived from MDA-MB-231 Cells in Microgravity.
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DOI：
10.1007/s10930-020-09949-2
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Wan Y
中科院分区：
文献类型：
--
作者：
Chen Y;Xue F;Russo A;Wan Y
三阴性乳腺癌（TNBC）患者的预后相对较差，无法从内分泌和/或靶向治疗中获益。人们已经付出了相当大的努力来阐明其分子机制和潜在的诊断/治疗靶点。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，并且通常无效。相比之下，在实验室环境中通过控制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是简单、明确和有效的。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，转移和耐药性。确定使癌细胞向侵袭性较低的表型转变的关键分子可能有助于未来的TNBC研究。我们专注于在微重力下从TNBC MDA-MB-231细胞衍生的细胞外囊泡（EV），其通过在细胞之间运输信号分子来介导细胞间通信。我们的研究结果表明，与全重力下的电池相比，微重力下EV释放速率降低，而平均EV尺寸增加。此外，我们发现EV在分析差异表达蛋白质方面可能优于细胞，特别是那些下调的蛋白质，并且在完整细胞内容物的分析中通常未被识别或被忽视的蛋白质。上级。EV和细胞的蛋白质组学分析进一步揭示了微重力下与GTP酶和MDA-MB-231细胞增殖的显著相关性。总之，我们的研究结果将进一步激发深入的相关癌症生物学研究和后续的临床研究。
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.
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影响因子：
3
作者：
Jhala, Dhwani V.;Kale, Raosaheb K.;Singh, Rana P.
通讯作者：
Singh, Rana P.
影响因子：
--
作者：
Barfeld SJ;Fazli L;Persson M;Marjavaara L;Urbanucci A;Kaukoniemi KM;Rennie PS;Ceder Y;Chabes A;Visakorpi T;Mills IG
通讯作者：
Mills IG
影响因子：
4.6
作者：
Michaletti A;Gioia M;Tarantino U;Zolla L
通讯作者：
Zolla L
影响因子：
3.5
作者：
Laulagnier, K;Grand, D;Record, M
通讯作者：
Record, M
三阴性乳腺癌：治疗挑战和解决方案。
DOI：
10.2147/bctt.s69488
发表时间：
2016
期刊：
Breast cancer (Dove Medical Press)
影响因子：
--
作者：
Collignon J;Lousberg L;Schroeder H;Jerusalem G
通讯作者：
Jerusalem G