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| Home > Publications database > Characterisation and comparison ofsmall extracellular vesicles after irradiationwith X-rays versus Carbon ions |
| Home > Publications database > Characterisation and comparison ofsmall extracellular vesicles after irradiationwith X-rays versus Carbon ions |
| Master Thesis | DKFZ-2021-02541 |
2021
Abstract: Pancreatic cancer is one of the most aggressive cancer types with poor prognosisdue to treatment resistance. Small extracellular vesicles (sEVs) are secreted byalmost all cell types and have been shown to be involved in several steps of cancerprogression and treatment resistance. To date, only a limited number of studiesinvestigated the effect of irradiation, especially heavy charged particle irradiation,on sEV secretion and composition. In this thesis, sEVs were isolated from twopancreatic cancer cell lines (Panc01, KPC) after irradiation with X-rays or carbonions. It was observed that both irradiation modalities stimulate the biogenesis andrelease of sEVs without influencing their size. Moreover, a connection betweenthe autophagy pathway and sEV biogenesis was observed. Investigation of theprotein content pointed at a change in sEV composition after irradiation, sincethe expression of several sEV markers and proteins increased after irradiation.In addition, double strand DNA (dsDNA) associated with sEVs was extensivelyexamined. It was found that the amount of dsDNA increased with increasingdose until 6Gy (X-rays) or 3Gy (Carbon ions), possibly indicating an activationof a degradation mechanisms at higher doses. Following experiments showed thatthe dsDNA was predominately localised on the surface of sEVs. Shedding lighton the effects of radiotherapy (X-rays vs carbon ions) on sEV composition is afirst step towards unlocking the full potential of sEVs in radiotherapy-associatedprognosis for pancreatic cancer, and unravelling new potential target for combinedtherapies.
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