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27.11.2018 | Preclinical study

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

verfasst von: Tatiana Shtam, Stanislav Naryzhny, Roman Samsonov, David Karasik, Igor Mizgirev, Artur Kopylov, Elena Petrenko, Yana Zabrodskaya, Roman Kamyshinsky, Daniil Nikitin, Maxim Sorokin, Anton Buzdin, Hava Gil-Henn, Anastasia Malek

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2019

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Abstract

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.

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Titel: Plasma exosomes stimulate breast cancer metastasis through surface interactions and activation of FAK signaling
verfasst von: Tatiana Shtam
Stanislav Naryzhny
Roman Samsonov
David Karasik
Igor Mizgirev
Artur Kopylov
Elena Petrenko
Yana Zabrodskaya
Roman Kamyshinsky
Daniil Nikitin
Maxim Sorokin
Anton Buzdin
Hava Gil-Henn
Anastasia Malek
Publikationsdatum: 27.11.2018
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2019
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-5043-0

Springer Medizin

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