As illustrated by the new ESC Guidelines on cardio-oncology, the increased risk of CVD in patients with cancer is well established. But are the roles also reversed – can CVD increase cancer risk?
Results presented today by MD PhD candidate Tal Caller (Sheba Medical Center, School of Medicine - Tel Aviv University, Israel) suggest a mechanistic link between heart disease and tumour growth, which is mediated by cardiac extracellular vesicles (EVs). In the first part of their study, they characterised EVs from isolated cardiac mesenchymal stromal cells following myocardial infarction (MI) or sham-MI in mice. Proteomic and biological-process analysis revealed a distinctive profile of EVs after MI, with more EV-encapsulated proteins related to inflammation, angiogenesis and cell cycle as compared to sham-operated mice. Purified and labelled EVs were found to target both breast and lung cancer cells in vitro. Furthermore, EVs from infarcted hearts facilitated cancer-cell proliferation more than sham-MI EVs and also accelerated cancer cell migration two-fold.
The second part of the study involved implanting lung or breast cancer cells into mice 10 days before MI, inhibiting EV production, and monitoring tumour growth with ultrasound. MI significantly stimulated lung cancer growth, while EV inhibition with the exosome inhibitor, GW4869, markedly attenuated this tumourigenic effect. In addition, an inverse correlation between LVEF and the volume of lung and breast tumours was observed, which was attenuated by GW4869.
According to the authors, these findings represent the first demonstration that cardiac mesenchymal stromal cells from infarcted and failing hearts secrete EVs that can target tumour cells and accelerate their growth. In terms of clinical implications, they propose that EVs could be possible therapeutic targets in patients with concomitant CVD and cancer.
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