Proton Compared to X-Irradiation Induces Different Protein Profiles in Oral Cancer Cells and Their Derived Extracellular Vesicles

• Published in: International journal of molecular sciences Vol. 24; no. 23; p. 16983
• Main Authors: Juvkam, Inga Solgård, Zlygosteva, Olga, Sitarz, Mateusz, Thiede, Bernd, Sørensen, Brita Singers, Malinen, Eirik, Edin, Nina Jeppesen, Søland, Tine Merete, Galtung, Hilde Kanli
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2023
• Subjects: Apoptosis; Cancer therapies; Cell adhesion & migration; Cell cycle; Cell death; DNA damage; DNA repair; Extracellular vesicles; Mass spectrometry; non-targeted effects of radiation; Oral cancer; oral squamous cell carcinoma; Proteins; Protons; Radiation therapy; Squamous cell carcinoma; X-rays; Norway; Germany; protons; oral squamous cell carcinoma; extracellular vesicles; X-rays; non-targeted effects of radiation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms242316983

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.