Cetuximab modifies the release and protein content of tumor microvesicles from head and neck squamous cell carcinoma cells: What are the consequences on endothelial cells?

Cancer cells can release extracellular vesicles (EVs) of different sizes under stress conditions. Among the EVs, microvesicles (MVs), which have a size between 50 and 1000 nm, are bounded by a membrane lipid bilayer, exhibit proteins at their surface, and enclose some soluble proteins. MVs can interact with surrounding cells present in the tumor microenvironment to favor tumor resistance. Indeed, they can transport some oncoproteins such as epidermal growth factor receptor (EGFR) and modify phenotype of endothelial cells (ECs). Even if their role in cell communication is well established, the understanding of anticancer treatments on their release and their protein content change are of particular importance. In this work, we showed that head and neck squamous cell carcinoma (HNSCC) cells exposed to cetuximab, monoclonal antibody targeting EGFR, can modulate EGFR expression of MVs. Moreover, this work emphasizes the effect of cetuximab on the shedding and content of MVs by HNSCC cells as well as their interaction with ECs. Consequently, MVs can be used as surrogate markers for predicting the efficacy of anti-EGFR therapies. Finally, the release of MVs after treatment must be envisaged as a resistance mechanism and must be considered in the future to evaluate the effect of therapy on the tumor microenvironment.