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Proteomic Analysis of Extracellular Vesicles Derived from MDA-MB-231 Cells in Microgravity

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Abstract

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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Data Availability

Data are available by request from the author for correspondence.

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Acknowledgements

This work was partially supported by Binghamton University Faculty Startup Fund 910252-35, Binghamton University S3IP award ADLG195, and NIH subward 1R01CA230339-01.

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Y.C., F.X., and Y. W. participated in the conceptualization and protocols; Y.C., and F.X. produced the data; all authors analyzed and interpreted the data. All authors prepared the manuscript and approved the final version of the manuscript.

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Correspondence to Yuan Wan.

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Chen, Y., Xue, F., Russo, A. et al. Proteomic Analysis of Extracellular Vesicles Derived from MDA-MB-231 Cells in Microgravity. Protein J 40, 108–118 (2021). https://doi.org/10.1007/s10930-020-09949-2

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