Hypertrophic cardiomyocytes promote breast cancer progression through exosomal miRNA and proteins

Evidence from epidemiological and mechanistic studies suggests that a variety of cardiovascular diseases are associated with tumour development. However, which cell types in the diseased heart are involved in the promotion of tumour progression remains poorly understood. In this study, the role of exosomes from hypertrophic cardiomyocytes in tumour progression was investigated. A model of cardiac hypertrophy was generated in mice using transverse aortic constriction (TAC). Breast cancer cells were then implanted in model animals. Exosomes derived from AC16 cardiomyocytes treated with Ang II to induce hypertrophic growth were subsequently injected into nude mice in which breast cancer cells had previously been implanted. The results showed that exosomes from hypertrophic cardiomyocytes promoted breast cancer progression. Furthermore, transcriptome sequencing and mass spectrometric analysis demonstrated that miR-362-5p, S100A7, and S100A8 were upregulated in exosomes derived from Ang II-treated AC16 cells, which promoted the proliferation, invasion, and migration of breast cancer cells. A retrospective clinical study showed that the expression of miR-362-5p, S100A7, and S100A8 was increased in plasma exosomes obtained from patients with cardiac hypertrophy. Notably, the levels of the three factors were observed to be associated with the extent of inflammation in patients with myocardial hypertrophy. Hypertrophic cardiomyocytes promote breast cancer progression through exosomes, and this effect is mediated by S100A7, S100A8, and miRNA-362-5p contained in the exosomes released from these cells.