N.N. Petrov National Medical Research Center of Oncology, Leningradskaya 68, St.-Petersburg, Russia, 197758.
Oncosystem Ltd., Lugovaya 4, Skolkovo Innovation Center, Moscow, Russia, 143026.
Breast Cancer Res Treat. 2019 Feb;174(1):129-141. doi: 10.1007/s10549-018-5043-0. Epub 2018 Nov 27.
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.
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.
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.
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.
癌细胞与周围健康组织的相互作用是乳腺癌（BC）转移进展的关键因素。已知细胞外囊泡（尤其是外泌体）参与癌症进展过程中的细胞间通讯。在本研究中，我们旨在评估循环血浆外泌体在 BC 转移扩散中的作用，并探讨这种现象的潜在分子机制。
将来自健康女性供体血浆的外泌体以不同浓度应用于 MDA-MB-231 和 MCF-7 细胞系的培养基中。通过随机迁移和 Transwell 侵袭实验检测 BC 细胞的迁移和侵袭特性，并在体内斑马鱼模型中证明血浆外泌体对 BC 细胞转移扩散的影响。为了揭示血浆外泌体与 BC 细胞相互作用的分子机制，我们对未经处理和酶处理的外泌体进行了比较，随后进行了质谱分析、基因本体论和途径分析。
血浆外泌体以剂量依赖的方式刺激 BC 细胞在体外的黏附特性、二维随机迁移和 Transwell 侵袭，以及体内转移扩散。这种刺激作用是通过外泌体表面蛋白与 BC 细胞的相互作用以及肿瘤细胞中粘着斑激酶（FAK）信号的激活介导的。
血浆外泌体具有刺激 BC 细胞促进转移特性的能力。正常血浆外泌体的这种促转移特性可能对疾病的进程及其预后产生影响。
