Cellular plasticity upon proton irradiation determines tumor cell radiosensitivity

Novel particle therapy was implemented into standard-of-care for cancer patients during the last years. However, experimental studies investigating cellular and molecular mechanisms are lacking although prognostic biomarker are urgently needed. The cancer stem cell (CSC)-related marker aldehyde dehydrogenase (ALDH) is known to impact on prostate cancer radiosensitivity through affecting defense against reactive oxygen species (ROS), reducing DNA damage repair and increasing cell survival. Surprisingly, we could show in a previous study that ionizing radiation itself enriches for ALDH-positive CSCs in a time- and dose-dependent manner through alteration in histone methylation. Within the present study, we investigated CSC marker dynamics upon proton beam irradiation and hypothesized that this novel particle therapy may have increased CSC targeting potential due to its increased ionization potential compared to conventional photon irradiation. However, we found that proton irradiation is affecting cellular dynamics and escape from cell death. Sham, proton treated and photon treated samples were made available to compare effects of proton irradiation and photon irradiation on multiple human tumour cell lines. Majority of samples were collected after 7 days of irradiation. Some samples were collected after 4 and 12 hours of irradiation. Up to 3 replicates exist for majority of the samples.