Role of plasma extracellular vesicles in lung cancer pre-metastatic niche formation

Lung cancer is the deadliest cancer worldwide, primarily due to metastatic spread. Tumor-derived extracellular vesicles (EVs) play a crucial role in the formation of pre-metastatic niches (pMNs), facilitating the spread and expansion of circulating cancer cells. So far, little is known about the role of plasma EVs in lung cancer pMN formation. We aim to elucidate the EV role in pMN formation and identify new prognostic biomarkers for early-stage lung cancer.Plasma-derived EVs were obtained by ultracentrifugation from early-stage lung cancer patients who survived at 5 years (ESA-EVs) and patients who died within two years (ESD-EVs). Heavy-smokers cancer free individuals were used as control (HS-EVs). Functional in vitro experiments on endothelial cells were carried out using 15ug of EVs from different groups for 48h. We observed that ESD-EVs significantly induced a “pro-inflammatory” endothelial phenotype. Characterization of ESD-EV revealed higher levels of miR-29 and C4a compared to ESA and HS-EVs. Concomitant miR-29 transfection and C4a administration in endothelial cells recapitulated the pro-inflammatory activation observed with EVs. In conclusion, we showed that plasma EVs could drive lung pMN formation, conferring a pro-inflammatory phenotype to endothelial cells to favour metastasis outgrowth