Characterisation of exosomes after in vitro and in vivo irradiation as markers of radiation exposure. Final report

Exosomes are a class of extracellular vesicles released by the vast majority of cell types. They contain proteins, lipids and nucleic acids. Initially, exosomes were seen merely as instruments for expelling cellular components. However, it is now also known that exosomes are taken up by other cells and influence their phenotype, thus representing an element of cell-cell communication. In some tumour cell lines it has already been shown that ionising radiation alters the composition and function of exosomes (AP1). Studies on the influence of ionising radiation on exosome-mediated cell-cell communication of non-malignant normal cells are still largely lacking. In this project, radiation-induced changes in the protein and microRNA composition of exosomes from different non-malignant cell culture model systems (lymphocytes, fibroblasts, endothelial and epithelial cells, AP2-AP4) were identified. The protein changes were related to proteins in the exosomes as well as on their surface (AP3). Among others, changes were also detected in exosomes released from primary lymphocytes of healthy donors after ex vivo irradiation. To contrast these results with in vivo data, candidate proteins and microRNAs in exosomes from the blood of radiotherapy patients were investigated in AP5. Overall, this project showed that exosomal microRNA and protein signatures are altered after in vitro irradiation of donor cells in a cell type- and dose-specific manner. Changes in exosomal microRNA and protein composition were also observed after in vivo irradiation (radiotherapy patients). Since exosomes are characterised by their stability and also contain biological markers that are not always found in the corresponding body fluids, they could provide particularly sensitive and specific diagnostic signatures. The changes found here should be validated in other radiation-relevant populations to test their suitability as biomarkers for radiation exposure. For further understanding of radiation risks, potential functional differences of exosomes from irradiated and non-irradiated cells should also be assessed in a follow-up project.