Evaluation of colchicine effect on tumor-derived extracellular vesicles (tumor-EVs) and endothelial cell interaction

Cancer remains a leading global health challenge, with extracellular vesicles (EVs) playing a key role in tumor progression and metastasis by facilitating intercellular communication. Colchicine, a microtubule inhibitor with established anti-inflammatory and antiproliferative properties, has shown potential in modulating EV-cell interaction. This study explores colchicine’s ability to inhibit the internalization and dissemination of tumor-derived EVs, aiming to disrupt metastatic mechanisms. In vitro, using renal cancer stem cell-derived EVs (G7-EVs) and both physiological and cancer endothelial cell models (HMEC and EcK), we demonstrate that colchicine significantly reduces G7-EV uptake, particularly in tumor endothelium, in a dose-dependent manner. Further analysis revealed that this inhibition is independent of ICAM-1/CD54 and integrin modulation, suggesting alternative mechanisms involving cytoskeletal and membrane lipid dynamics requiring further investigations. The in vivo biodistribution study here conducted, confirmed colchicine’s effect, showing reduced G7-EV accumulation in tumor-EV target organs such as the lung, liver, and kidney. These findings provide novel insights into colchicine’s potential to interfere with EV-driven tumor progression. Given its affordability, established clinical use, and non-invasive administration, colchicine represents a promising candidate for further investigation as an anti-metastatic therapy.