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| Home > Publications database > Eects of 12C Ion and X-ray Irradiation on theBiogenesis of small Extracellular Vesicles withFocus on the Autophagy Pathway |
| Home > Publications database > Eects of 12C Ion and X-ray Irradiation on theBiogenesis of small Extracellular Vesicles withFocus on the Autophagy Pathway |
| Master Thesis | DKFZ-2022-02711 |
2022
Abstract: All cells secrete small Extracellular Vesicles (sEVs). Those nanoparticles playan important role in cell-cell communication since their cargos induce phenotypealterations in recipient cells. Interestingly, radiotherapy not only stimulates sEVbiogenesis but also alters their loading, a process potentially related to the autophagy pathway.This thesis aims at investigating the eects of autophagy inhibitors combined withirradiation on the sEV biogenesis and their metastatic properties in a pancreaticcancer model (KPC cells). For this purpose, the autophagy pathway was inhibitedwith 1 µM Chloroquine (CQ) or 0.25 mM 3-Methyladenin (3-MA) in combinationwith 8 Gy X-rays or 3 Gy 12C ion irradiation.It was demonstrated that CQ, by inhibiting the autophagosome-lysosome fusion,increased the intracellular sEV formation in multivesicular bodies in combination with irradiation. Contrary, 3-MA, an inhibitor of the autophagy initiation,blocked the sEV biogenesis, even with applied radiation.Finally, the investigated ability of sEVs to signicantly aect the metastatic stateof recipient cells, depending on the drug and irradiation combination of the original cells, underlined the therapeutical potential of sEVs and the autophagy inhibitors in cancer treatment.
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