Effect of macrophage-derived extracellular vesicles on a colorectal cancer cell line

Abstract

[eng] Colorectal cancer (CRC) is a worldwide health burden. A significant increase in cases is expected in a few years and the need of finding new and more reliable approaches is growing. Macrophages (Mφ) are immune cells that play a crucial role in innate and adaptive immunity. Depending on the microenvironment and signals present, Mφ can polarize into either M1 (pro-inflammatory) or M2 (antiinflammatory) phenotypes. Mφ have been shown to play key roles in the development and progression or inhibition of various diseases, including cancer. Extracellular vesicles (EVs) are lipidic nanoparticles that have been shown to exert similar functions as their parental cells. Then, Mφ-derived EVs could stimulate tumour progression by promoting immunosuppression, angiogenesis, invasion, and metastasis as well. This work aimed to investigate the effect of EVs derived from polarized Mφ on a CRC cell line. Monocytes were extracted from buffy coats and cultured in RPMI medium with platelet lysate (PL). After 6 days of seeding, Mφ were differentiated into M1 and M2 using INF-γ and IL-4/IL-13, respectively. The medium containing M1 or M2-derived EVs was collected and the nanovesicles were isolated by size exclusion chromatography. The size and concentration of the EVs were characterized. The presence of EVs markers (CD9, CD63) was assessed by Western Blot and Dot Blot. Finally, EVs derived from the polarized Mφ were added onto SW480 cells and their effect on cell viability and cell cycle was evaluated. Overall, we observed that CRC cells responded differentially to EVs isolated from the M1 and M2 Mφ. In summary, the use of Mφ-derived EVs for the treatment of cancers deserves further study as it could benefit from interesting traits of EVs such as low immunogenicity, nontoxicity, and ability to pass through tissue barriers.