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Research Article

Caveolin-1-containing extracellular vesicles transport adhesion proteins and promote malignancy in breast cancer cell lines

    America Campos

    Laboratory of Cellular Communication, Center for Studies of Exercise, Metabolism & Cancer (CEMC), Program of Cell & Molecular Biology, Faculty of Medicine, Universidad de Chile, Santiago, Chile

    Fundación Ciencia & Vida, Santiago, Chile

    Advanced Center for Chronic Diseases (ACCDiS), Independencia, Santiago, Chile

    ,
    Carlos Salomon

    Centro de Investigación Biomédica, Facultad de Medicina, Universidad de los Andes, Santiago, Chile

    Exosome Biology Laboratory, UQ Centre for Clinical Research, Brisbane, Australia

    ,
    Rocio Bustos

    Fundación Ciencia & Vida, Santiago, Chile

    ,
    Jorge Díaz

    Laboratory of Cellular Communication, Center for Studies of Exercise, Metabolism & Cancer (CEMC), Program of Cell & Molecular Biology, Faculty of Medicine, Universidad de Chile, Santiago, Chile

    Advanced Center for Chronic Diseases (ACCDiS), Independencia, Santiago, Chile

    ,
    Samuel Martínez

    Laboratory of Cellular Communication, Center for Studies of Exercise, Metabolism & Cancer (CEMC), Program of Cell & Molecular Biology, Faculty of Medicine, Universidad de Chile, Santiago, Chile

    Advanced Center for Chronic Diseases (ACCDiS), Independencia, Santiago, Chile

    ,
    Veronica Silva

    Fundación Ciencia & Vida, Santiago, Chile

    ,
    Constanza Reyes

    Fundación Ciencia & Vida, Santiago, Chile

    ,
    Natalia Díaz-Valdivia

    Laboratory of Cellular Communication, Center for Studies of Exercise, Metabolism & Cancer (CEMC), Program of Cell & Molecular Biology, Faculty of Medicine, Universidad de Chile, Santiago, Chile

    Advanced Center for Chronic Diseases (ACCDiS), Independencia, Santiago, Chile

    ,
    Manuel Varas-Godoy

    Department of Clinical Biochemistry & Immunology, Faculty of Pharmacy, University of Concepción, Bío Bío Region, Chile

    ,
    Lorena Lobos-González

    **Author for correspondence: Tel.: +56 2978 6371;

    E-mail Address: llobos@udd.cl

    Fundación Ciencia & Vida, Santiago, Chile

    Advanced Center for Chronic Diseases (ACCDiS), Independencia, Santiago, Chile

    Centro de Medicina Regenerativa, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, La Barnechea, Santiago, Chile

    &
    Andrew FG Quest

    *Author for correspondence: Tel.: +56 2978 6371;

    E-mail Address: aquest@med.uchile.cl

    Laboratory of Cellular Communication, Center for Studies of Exercise, Metabolism & Cancer (CEMC), Program of Cell & Molecular Biology, Faculty of Medicine, Universidad de Chile, Santiago, Chile

    Advanced Center for Chronic Diseases (ACCDiS), Independencia, Santiago, Chile

    Published Online:https://doi.org/10.2217/nnm-2018-0094

    Breast cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths in women worldwide, whereby mortality is largely attributable to the development of distant metastasis. Caveolin-1 (CAV1) is a multifunctional membrane protein that is typically upregulated in the final stages of cancer and promotes migration and invasion of tumor cells. Elevated levels of CAV1 have been detected in extracellular vesicles (EVs) from advanced cancer patients. EVs are lipid enclosed vesicular structures that contain bioactive proteins, DNA and RNAs, which can be transferred to other cells and promote metastasis. Therefore, we hypothesized that CAV1 containing EVs released from breast cancer cells may enhance migration and invasion of recipient cells. EVs were purified from conditioned media of MDA-MB-231 wild-type (WT), MDA-MB-231 (shCAV1; possessing the plasmid pLKO.1 encoding a ‘small hairpin’ directed against CAV1) and MDA-MB-231 (shC) short hairpin control cells. Nanoparticle tracking analysis revealed an average particle size of 40–350 nm for all preparations. As anticipated, CAV1 was detected in MDA-MB-231 WT and shC EVs, but not in MDA-MB-231 (shCAV1) EVs. Mass spectrometry analysis revealed the presence of specific cell adhesion-related proteins, such as Cyr61, tenascin (TNC) and S100A9 only in WT and shC, but not in shCAV1 EVs. Importantly, EVs containing CAV1 promoted migration and invasion of cells lacking CAV1. We conclude that the presence of CAV1 in EVs from metastatic breast cancer cells is associated with enhanced migration and invasiveness of recipient cells in vitro, suggesting that intercellular communication promoted by EVs containing CAV1 will likely favor metastasis in vivo.

    Papers of special note have been highlighted as: • of interest

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