CD44‑hyaluronan axis plays a role in the interactions between colon cancer‑derived extracellular vesicles and human monocytes

During tumor progression, monocytes circulating in the blood or infiltrating tissue may be exposed to tumor-derived extracellular vesicles (TEVs). The first stage of such interactions involves binding of TEVs to the surface of monocytes, followed by their internalization. The present study examines the role of CD44 molecules in the interactions between monocytes and EVs derived from colon cancer cell lines (HCT116 and SW1116). The efficiency of the attachment and engulfment of TEVs by monocytes is linked to the number of TEVs and time of exposure/interaction. The two investigated TEVs, TEVs(HCT116) and TEVs(SW1116), originating from HCT116 and SW1116 cells, respectively, differ in hyaluronan (HA) cargo, which reflects HA secretion by parental cancer cells. HA-rich TEVs(HCT116) are internalized more effectively in comparison with HA-low TEVs(SW1116). Blocking of CD44 molecules on monocytes by anti-CD44 monoclonal antibody significantly decreased the engulfment of TEVs(HCT116) but not that of TEVs(SW1116) after 30 min contact, suggesting the involvement of the HA-CD44 axis. The three subsets of monocytes, classical, intermediate and non-classical, characterized by gradual changes in the expression of CD14 and CD16 markers, also differ in the expression of CD44. The highest expression of CD44 molecules was observed in the intermediate monocyte subset. Blocking of CD44 molecules decreased the internalization of HA-rich TEVs in all three subsets, which is associated with CD44 expression level. It was hypothesized that HA carried by TEVs, potentially as a component of the ‘corona’ coating, may facilitate the interaction between subsets of monocytes and TEVs, which may influence the fate of TEVs (such as the rate of TEVs adhesion and engulfment) and change monocyte activity.