Extracellular vesicles from hypertrophic cardiomyocytes promote breast cancer progression

Abstract

Several cardiovascular diseases are associated with tumor development. But the mechanisms underlying how the hypertrophic heart promotes tumor progression remain unknown. Here, we show that extracellular vesicles from hypertrophic cardiomyocytes facilitate cancer progression. Following transverse aortic constriction to induce cardiac hypertrophy, 4T1-Luc cells are orthotopically implanted into mice. Concurrently, AC16 cells are treated with angiotensin II, and extracellular vesicles isolated from these cells are administered to BALB/c nude mice previously implanted with MDA-MB-231 cells in their mammary fat pads. Both transverse aortic constriction-operated mice and mice receiving extracellular vesicles from angiotensin II-treated AC16 cells exhibit accelerated breast cancer progression; however, treatment with GW4869, an extracellular-vesicles-release inhibitor, suppresses this effect. Transcriptome sequencing and mass spectrometry indicate that the expression of miR-362-5p, S100A7, and S100A8 is upregulated in these extracellular vesicles, which significantly boosts breast cancer cell proliferation, invasion, and migration. Importantly, miR-362-5p, S100A7, and S100A8 levels are elevated in plasma extracellular vesicles from patients with myocardial hypertrophy and are positively correlated with inflammatory indices. Our research identifies the specific factors in hypertrophic cardiomyocytes that drive tumor progression, laying a theoretical foundation for future targeted intervention and prevention.