Cardiomyocyte-derived exosomes: linking heart failure to tumour progression

Background It has been shown that heart failure (HF) promotes tumour growth circulating factors. Exosomes, extracellular vesicles (30–150 nm) with lipid bilayer membranes, mediate intercellular communication. We hypothesize that exosomes from failing hearts deliver oncogenic signals to tumours through the bloodstream. Methods To track cardiac exosomes reaching tumours, we used transgenic (TG-αMHC-STOP-CD63NanoLuc) mice engineered to express CD63-NanoLuc allowing to track cardiomyocyte-derived exosomes for our studies. E0771 cancer cells were inoculated into the mammary fat pad of the experimental mice. Then, mice underwent myocardial infarction (MI) or sham surgery, with cardiac function assessed weekly by echocardiography. Three weeks post-MI, tissues, including tumours, were harvested for luciferase signal measurement. Exosomes in plasma and cardiac tissues were quantified by nanoparticle tracking analysis, and tetraspanin markers (CD9, CD63, CD81) were analysed using SP-IRIS (Leperchaun). Results MI mice exhibited a 2.3-fold reduction in ejection fraction (p < 0.0001), a 1.6-fold increase in tumour weight (p = 0.141), and a 2.4-fold increase in tumour volume (p = 0.0001) compared to sham mice. Tumour luciferase activity was detected in both groups and was significantly correlated with heart luciferase activity. SP-IRIS analysis in cardiac tissues revealed that exosomes with CD63/CD81/CD9 markers constituted 13.63% of the total population of exosomes in MI mice versus 7.5% in sham mice. Conclusion These data demonstrate that cardiomyocyte-derived exosomes reach distant breast cancer tumours, and this potentially represents a novel route of crosstalk between the heart and tumours. The increased proportion of CD63/CD81/CD9-positive exosomes in failing cardiac tissue highlights the presence of HF-induced alterations in exosomes. Future work will analyse the cargo of these exosomes to elucidate their oncogenic potential.