Axis 2, Team 3 | Impact of environmental contaminants on intercellular communication via extracellular vesicles (EVs)

 

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Chemically-induced membrane remodeling might also affect intercellular communication, in particular through changes of extracellular vesicle (EV) amount and composition. EVs have been described to play major roles in intercellular crosstalk. These EVs are made up of microparticles (MPs, also named microvesicles), exosomes and apoptotic bodies, which exhibit specific sizes and sedimentation properties. The different types of EVs would possess specific functions. Circulating EVs released from various cell types are present in healthy individuals, and their number and composition vary, depending on the type of stimulation and pathophysiology of parental cells. In this context, it has been proposed that EVs may constitute diagnostic biomarkers for cancer and other diseases, such as cardiovascular or infectious diseases.
EVs contain lipids, proteins, RNAs and microRNAs (miRNAs) acting as vectors of information to regulate functions of target cells. For example, upon liver injury induced by alcohol consumption, viral infection or under pathological conditions (diabetes, obesity and dyslipidemia), hepatic cells could produce EVs leading to liver disease development and progression. This axis therefore aims at determining the impact of environmental contaminants on EV production by hepatic and other cells (endothelial cells, macrophages), in order to identify early and very weakly invasive biomarkers for an excess hepatic cancer risk following exposure to environmental pollutants (Anses project “EXOCELL”).