Autor: |
Juvkam IS; Institute of Oral Biology, Faculty of Dentistry, University of Oslo, 0372 Oslo, Norway.; Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, Norway., Zlygosteva O; Department of Physics, Faculty of Mathematics and Natural Sciences, University of Oslo, 0371 Oslo, Norway., Sitarz M; Danish Centre for Particle Therapy, Aarhus University Hospital, 8200 Aarhus, Denmark., Thiede B; Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 0371 Oslo, Norway., Sørensen BS; Danish Centre for Particle Therapy, Aarhus University Hospital, 8200 Aarhus, Denmark.; Department of Experimental Clinical Oncology, Aarhus University Hospital, 8200 Aarhus, Denmark., Malinen E; Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, Norway.; Department of Physics, Faculty of Mathematics and Natural Sciences, University of Oslo, 0371 Oslo, Norway., Edin NJ; Department of Physics, Faculty of Mathematics and Natural Sciences, University of Oslo, 0371 Oslo, Norway., Søland TM; Institute of Oral Biology, Faculty of Dentistry, University of Oslo, 0372 Oslo, Norway.; Department of Pathology, Oslo University Hospital, 0372 Oslo, Norway., Galtung HK; Institute of Oral Biology, Faculty of Dentistry, University of Oslo, 0372 Oslo, Norway. |
Abstrakt: |
Extracellular vesicles (EVs) are membrane-bound particles released from cells, and their cargo can alter the function of recipient cells. EVs from X-irradiated cells have been shown to play a likely role in non-targeted effects. However, EVs derived from proton irradiated cells have not yet been studied. We aimed to investigate the proteome of EVs and their cell of origin after proton or X-irradiation. The EVs were derived from a human oral squamous cell carcinoma (OSCC) cell line exposed to 0, 4, or 8 Gy from either protons or X-rays. The EVs and irradiated OSCC cells underwent liquid chromatography-mass spectrometry for protein identification. Interestingly, we found different protein profiles both in the EVs and in the OSCC cells after proton irradiation compared to X-irradiation. In the EVs, we found that protons cause a downregulation of proteins involved in cell growth and DNA damage response compared to X-rays. In the OSCC cells, proton and X-irradiation induced dissimilar cell death pathways and distinct DNA damage repair systems. These results are of potential importance for understanding how non-targeted effects in normal tissue can be limited and for future implementation of proton therapy in the clinic. |