Stimulation of metastatic activity of breast cancer cells by plasma exosomes


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Abstract

Background. Malignant phenotype of cancer cells and metastatic potency of the tumor are determined by genetic factors. In addition, normal biological environment, including the nano-vesicles or exosomes, plays an important role in regulation of the structural and functional characteristics of malignant cells. Objective: presented study was aimed to evaluate mechanisms and to estimate effect of interaction of plasma exosomes and breast cancer cells in experimental conditions. Materials and methods. We used breast cancer cell culture MDA-MB-231 and exosomes isolated from plasma and cultural medium. Exosomes were analyzed by dynamic light scattering method and western blotting. Functional effects of exosomes were evaluated in in vitro and in vivo models. Results. In the present study we demonstrated that plasma exosomes stimulate the adhesion and the motility of breast cancer cells and induce the process of metastatic dissemination. Contact interaction of exosomes with cell surface is sufficient for stimulatory effect that is mediated by exosomal fibronectin and FAK-dependent signaling cascade. Conclusions. Further investigation of plasma exosomes structure and functions is required to better understand their input in regulation of malignant cell phenotype. This research has a potential to provide novel approaches for cancer therapy.

About the authors

R. B. Samsonov

Oncosystem, Ltd; Petrov Institute of Oncology

Author for correspondence.
Russian Federation

I. M. Kovalenko

Petrov Institute of Oncology

Russian Federation

D. A. Vasilyev

Petrov Institute of Oncology

Russian Federation

E. V. Tsyrlina

Petrov Institute of Oncology

Russian Federation

G. A. Dashan

Petrov Institute of Oncology

Russian Federation

Ch. . Shochat-Carvalho

Bar-Ilan University

Russian Federation

D. . Karasik

Bar-Ilan University

Russian Federation

L. M. Berstein

Oncosystem, Ltd

Russian Federation

V. V. Lutynskij

Company Algimed, Ltd

Russian Federation

A. V. Malek

Oncosystem, Ltd; Petrov Institute of Oncology

Email: anastasia@malek.com
Russian Federation

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