Plasma exosomes stimulate breast cancer metastasis through surface interactions and activation of FAK signaling

Purpose The interaction between malignant cells and surrounding healthy tissues is a critical factor in the metastatic progression of breast cancer (BC). Extracellular vesicles, especially exosomes, are known to be involved in inter-cellular communication during cancer progression. In the study pres...

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Bibliographic Details
Published in:Breast cancer research and treatment 2019-02, Vol.174 (1), p.129-141
Main Authors: Shtam, Tatiana, Naryzhny, Stanislav, Samsonov, Roman, Karasik, David, Mizgirev, Igor, Kopylov, Artur, Petrenko, Elena, Zabrodskaya, Yana, Kamyshinsky, Roman, Nikitin, Daniil, Sorokin, Maxim, Buzdin, Anton, Gil-Henn, Hava, Malek, Anastasia
Format: Article
Language:English
Subjects:
Analysis
Breast cancer
Cancer metastasis
Cancer research
Cell adhesion
Cell interactions
Development and progression
Exosomes
Extracellular vesicles
Focal adhesion kinase
Genes
Genetic research
Invasiveness
Kinases
Mass spectrometry
Mass spectroscopy
Medicine
Medicine & Public Health
Metastases
Metastasis
Molecular modelling
Oncology
Plasma
Preclinical Study
Proteins
Spectroscopy
Surface science
Tumor cells
Tumors
Women's health
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Summary:Purpose The interaction between malignant cells and surrounding healthy tissues is a critical factor in the metastatic progression of breast cancer (BC). Extracellular vesicles, especially exosomes, are known to be involved in inter-cellular communication during cancer progression. In the study presented herein, we aimed to evaluate the role of circulating plasma exosomes in the metastatic dissemination of BC and to investigate the underlying molecular mechanisms of this phenomenon. Methods Exosomes isolated from plasma of healthy female donors were applied in various concentrations into the medium of MDA-MB-231 and MCF-7 cell lines. Motility and invasive properties of BC cells were examined by random migration and Transwell invasion assays, and the effect of plasma exosomes on the metastatic dissemination of BC cells was demonstrated in an in vivo zebrafish model. To reveal the molecular mechanism of interaction between plasma exosomes and BC cells, a comparison between un-treated and enzymatically modified exosomes was performed, followed by mass spectrometry, gene ontology, and pathway analysis. Results Plasma exosomes stimulated the adhesive properties, two-dimensional random migration, and transwell invasion of BC cells in vitro as well as their in vivo metastatic dissemination in a dose-dependent manner. This stimulatory effect was mediated by interactions of surface exosome proteins with BC cells and consequent activation of focal adhesion kinase (FAK) signaling in the tumor cells. Conclusions Plasma exosomes have a potency to stimulate the metastasis-promoting properties of BC cells. This pro-metastatic property of normal plasma exosomes may have impact on the course of the disease and on its prognosis.
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-018-5043-0