AHA 2022: Extracellular vesicles in myocardial infarction promote tumor growth

Heart disease can be an independent risk factor for cancer (reverse cardiac oncology).

The cellular and molecular mechanisms linking heart disease to cancer remain elusive, and specific treatments are limited
.
We hypothesized that extracellular cardiac vesicles (cEVs) secreted by diseased hearts carry and propagate factors
that promote tumor growth.

Methods and results: We performed myocardial infarction (MI) or sham MI and 28-day follow-up
on female mice.
Echocardiography confirms left ventricular remodeling
.
To determine the role of cEVs in tumor growth, we focused on cardiac mesenchymal stromal cells (cMSCs), which play a central role
in cardiac repair, remodeling, and fibrosis.
Thus, we isolated cMSCs
from mouse hearts 10 or 28 days after MI or pseudoMI.
cMSCs after myocardial infarction secrete more small EVs
than cMSCs from pseudomyocardial infarction.
Proteomic analysis reveals unique features of cEV after myocardial infarction (Figure A).

Purified cMSC-EV targets breast and lung cancer cells
in vitro.
Scratch tests have shown that MI-cEV promotes cancer cell proliferation and migration twice as fast as fake MI cEV (Figure B, p=0.
0002).

Finally, 10 days before and after MI, lung or breast cancer cells are inoculated into the
hindlimb or breast pad.
Tumor growth
is monitored by serial ultrasound.
While MI stimulates tumor growth, the inhibition of EV by GW4869 significantly attenuates this effect (Figure C).

Conclusion: We demonstrated for the first time that EVs secreted by cMSCs from infarction and remodeling the heart target tumor cells and promote tumor growth
.
We recommend cEVs as potential mediators and therapeutic targets in patients with co-existing heart disease and cancer