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    Extracellular vesicles from young women's breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach.

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    Author
    Jordan, Kimberly R
    Hall, Jessica K
    Schedin, Troy
    Borakove, Michelle
    Xian, Jenny J
    Dzieciatkowska, Monika
    Lyons, Traci R
    Schedin, Pepper
    Hansen, Kirk C
    Borges, Virginia F
    Date
    2020-11-23
    Journal
    Breast Cancer Research : BCR
    Publisher
    Springer Nature
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1186/s13058-020-01363-x
    Abstract
    Background: Extracellular vesicles (EVs) are small membrane particles that contribute to cancer progression and metastases by transporting biologically significant proteins and nucleic acids. They may also serve as biomarkers of various disease states or important therapeutic targets. Breast cancer EVs have the potential to change the behavior of other cells in their microenvironment. However, the proteomic content of EVs isolated from young women’s breast cancer patients and the mechanisms underlying the influence of EVs on tumor cell behavior have not yet been reported. Methods: In our current translational studies, we compared the proteomic content of EVs isolated from invasive breast cancer cell lines and plasma samples from young women’s breast cancer (YWBC) patients and age-matched healthy donors using mass spectrometry. We analyzed the functionality of EVs in two dimensional tumor cell invasion assays and the gene expression changes in tumor cells after incubation with EVs. Results: We found that treatment with EVs from both invasive breast cancer cell lines and plasma of YWBC patients altered the invasive properties of non-invasive breast cancer cells. Proteomics identified differences between EVs from YWBC patients and healthy donors that correlated with their altered function. Further, we identified gene expression changes in non-invasive breast cancer cells after treatment with EVs that implicate the Focal Adhesion Kinase (FAK) signaling pathway as a potential targetable pathway affected by breast cancer-derived EVs. Conclusions: Our results suggest that the proteome of EVs from breast cancer patients reflects their functionality in tumor motility assays and may help elucidate the role of EVs in breast cancer progression.
    Sponsors
    The research in this publication is funded by the following grants: the DOD Idea Award W81XWH-13-1-0078, the Breast Cancer Research Foundation-AACR Grant for Translational Research #09-06-26BORG, the Grohne Family Foundation, and the Conner Family Foundation to VB, and the following shared resource grants: NIH/NCI CCSG P30CA046934 (Protein Production/Mab/Tissue Culture Shared Resource) and the NIH/NCRR Colorado CTSI Grant UL1 RR025780.
    Keyword
    Breast cancer
    Exosomes
    Extracellular vesicles
    Nanoparticles
    Proteomics
    Young women’s breast cancer
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/14156
    ae974a485f413a2113503eed53cd6c53
    10.1186/s13058-020-01363-x
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