Exosome secretion and cellular response of DU145 and PC3 after exposure to alpha radiation

Abstract

Exosomes are spherical membrane nanovesicles secreted from cells, and they play an important role in tumor immune response, metastasis, angiogenesis, and survival. Studies investigating exosomes isolated from cells exposed to photon radiation commonly used in conventional radiotherapy demonstrate the influence of this type of radiation on exosome characteristics and secretion. There is currently no research investigating the effects of densely ionizing particles such as protons and alpha radiation on exosomes. Thus we have evaluated the cellular response of human prostate cancer cells exposed to 0, 2, and 6 Gy of alpha radiation emitted from the Am-241 source. Irradiated PC3 and DU145 cell lines, characterized by differences in radiosensitivity, were studied using apoptosis, LDH, and IL-6 assays. Additionally, the corresponding concentration and size of isolated exosomes were measured using NTA. We found that exposure to ionizing radiation resulted in gross changes in viability and cell damage. There were increased amounts of apoptotic or necrotic cells as a function of radiation dose. We demonstrated that irradiated PC3 cells secrete higher quantities of exosomes compared to DU145 cells. Additionally, we also found no statistical difference in exosome size for control and irradiated cells.

Brownian Motion Influence on AFM Exosomes’ Size Measurements

“…The presence of exosomes in the sample was confirmed by fluorescence measurement of NTA with CD9 antibodies (cfr. [ 25 ]).…”

Physical modulation of mesenchymal stem cell exosomes: A new perspective for regenerative medicine

“…First, numerous studies have reported that diverse physical stimulations can alter the composition and biological properties of exosomes. Several researchers have provided evidence that the bioactivity and biological composition of exosomes are influenced after exposure to ionizing radiation 72,80–82 . In addition, FSS, 83 microgravity, 84 substrate stiffness, 60 electrical stimulation 85,86 and ultrasound 65 have been proved to have the capacity to influence the bioactive cargo of exosomes, resulting in modifications to their functional characteristics.…”

“…Several researchers have provided evidence that the bioactivity and biological composition of exosomes are influenced after exposure to ionizing radiation. 72 , 80 , 81 , 82 In addition, FSS, 83 microgravity, 84 substrate stiffness, 60 electrical stimulation 85 , 86 and ultrasound 65 have been proved to have the capacity to influence the bioactive cargo of exosomes, resulting in modifications to their functional characteristics. Notably, a recent study proposed that further investigation is needed to determine the optimal settings of photobiomodulation (PBM) in the context of MSC‐Exo modification, 87 while another study evidenced that light‐emitting diode irradiation suppressed the angiogenic capacity of exosomes secreted by uterine adenocarcinoma cells.…”

“…An increasing number of studies have demonstrated the significant influence of ionizing radiation on the release and bio‐properties of exosomes derived from keratinocytes, 81 cancer cells 72 , 80 , 165 and other sources. 82 Consistently, ionizing radiation has also been shown to increase the secretion of MSC‐Exo.…”