Molecular And Functional Characterization Of Extracellular Vesicles Released By A Lymphocyte Line Transformed By Marek's Disease Virus
Résumé
Extracellular vesicles (EVs) emitted by cells allow cell-to-cell transmission of bioactive molecules (proteins, DNA, mRNA and/or microRNAs) leading to an exchange of informations between cells and a potential reprogramming of “recipient cells”. Tumor cells are able to release a significant amount of EVs that can influence tumor development, tumor growth, metastatic processes and resistance to cancer therapies. EVs produced by tumor cells are able to transmit signals to immune cells and thus contribute to the escape of cancer cells to the immune response and to the establishment of an immunosuppressive microenvironment favorable to tumor growth. Despite the identification of pro-oncogenic viral molecules, the processes leading to MDV-induced tumorigenesis remain poorly understood. We assessed the role of EVs produced by MDV-transformed lymphocytes in neoplastic mechanisms by specifying their impact on cell proliferation. Molecular characterization of EVs isolated from MDV tumor cells was performed by western blot and proteomic approach. We validated the presence of EV-specific markers, identified cellular biomolecules enriched in these EVs and showed that EVs do not contain viral proteins. Moreover, we demonstrated that EVs are rapidly internalized by recipient cells and that they are able to modulate avian immune cells proliferation. These EVs have indeed a pro-proliferative effect on splenic T cells and an antiproliferative effect on B cells isolated from bursa of Fabricius. These data suggest that EVs are able to transfer opposite signals to uninfected B and T cells, affecting their proliferation and therefore that they could contribute to transformation process.