Breast cancer is one of the most diagnosed tumours in the world, and it is localised close to heart tissue [1]. Extracellular vesicles (EVs) secreted by cancer, which are rich in oncoproteins and oncogenic factors, play a crucial role in tumor growth and spread [2]. Cancer cells produce these vesicles in significantly larger quantities than healthy cells [3]. EVs can easily cross biological barriers and reach any part of the body, including the heart, making it easier for them to transmit oncogenic material to healthy cells [4]. It is known that EVs can influence the function, viability, and morphology of vascular cells, but there is still a lack of information on their effects on cardiomyocytes [4]. Cardio-oncology is a new branch of science that explores the relationship between oncological and cardiovascular diseases [5]. However, there is still a lack of studies investigating the connection between these pathologies through cancer-secreted EVs [5]. For this reason, the aim of this work was to determine the effects of the extracellular vesicles secreted by the breast cancer on the function and viability of cardiovascular system cells.
EVs were purified from human breast adenocarcinoma MCF-7 cell conditioned media using centrifugation and polymer precipitation methods. EVs was characterised by size using dynamic light scattering method and nanoparticle tracking analysis, by total protein using Bradford assay and by total RNA using TRIzol reagent. To examine the effect of breast cancer EVs on the cardiovascular system we affected primary Wistar rat cardiomyocytes and human umbilical cord vascular endothelial cells HUVEC with MCF-7 EVs. The viability of affected cells was estimated by PrestoBlue assay and bioenergetic changes in mitochondria were detected using the Seahorse XFp analyser. Statistical analysis and visualisation were made with GraphPad 10 program.
We determined that both size MCF-7 EVs (small and large) inhibit HUVEC viability, migration and bioenergetics processes, however large EVs induced a higher-level inhibition of metabolism and mitochondrial respiration in cardiomyocytes.
The obtained results suggests that both size MCF-7 EVs inhibit HUVEC and cardiomyocytes functions and viability. Large EVs had a greater inhibitory effect on cardiomyocytes function and bioenergetic processes than small EVs. HUVEC functions was inhibited equally by EVs of both sizes. It is possible that such inhibition of cardiovascular system cells indicates that cancer-derived EVs promote inflammatory processes and oxidative stress within the cells, which can lead to functional changes in mitochondria, thereby inhibiting cellular respiration and energy production.