Proton-Induced Bystander Signaling Drives Cell-Type-Specific Proteomic Remodeling in Chondrocytes and Endothelial Cells
5 affiliations
- 1Department of Life and Environmental Physics, Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering, 077125 Magurele, Romania
- 2Faculty of Biology, University of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, Romania
- 3US EMerode, Plateform Proteogen Université de Caen Normandie, 14032 Caen, France
- 4Radiopharmaceutical Research Centre, Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering, 077125 Magurele, Romania
- 5Centre de recherche sur les Ions les Matériaux et la Photonique, Université de Caen Normandie, CEA, CNRS, ENSICAEN, UMR6252 CIMAP, Team Applications in Radiobiology with Accelerated Ions, 14000 Caen, France
Abstract
Background/Objectives: Radiation-induced bystander effects (RIBEs), whereby irradiated cells transmit biological signals to neighboring, non-irradiated cells, are a well-recognized phenomenon in radiobiology. However, proton-induced RIBEs remain incompletely understood. This study investigated the bystander responses elicited by proton-irradiated chondrosarcoma cells in non-irradiated chondrocytes and endothelial cells. Methods: T/C-28A2 chondrocytes and EA.hy926 endothelial cells were exposed to conditioned medium (CM) collected from SW1353 chondrosarcoma cells irradiated with protons at doses ranging from 0.1 to 2 Gy. Clonogenic survival and micronucleus (MN) assays were initially performed to assess the susceptibility of recipient cells to bystander signaling. Based on these findings, cell cycle distribution, reactive oxygen species (ROS) level, and proteomic profiles were subsequently analyzed under the most responsive experimental conditions. Results: CM from proton-irradiated chondrosarcoma cells induced significant but cell-type-specific bystander responses. Chondrocytes were most responsive to CM from cells irradiated with 0.1 Gy, exhibiting reduced clonogenic survival, increased micronucleus formation, and adaptive-like proteomic changes consistent with reduced proliferation and extracellular matrix remodeling. In contrast, endothelial cells responded predominantly to conditioned medium from 2 Gy irradiated cells, displaying reduced survival, increased genomic instability, cell cycle perturbations, persistent ROS accumulation, and extensive proteomic remodeling involving elevated levels of proteins associated with metabolism and DNA repair proteins. Network analysis further revealed cell-type-specific alterations in inflammatory, mitochondrial, and intracellular signaling pathways, highlighting distinct mechanisms underlying bystander response. Conclusions: Proton-induced bystander responses differed between the two recipient cell models and were associated with distinct proteomic profiles under the selected experimental conditions. These findings identify candidate proteins and pathways for further investigation but do not establish causal mechanisms or validated biomarkers. Further studies are needed to distinguish the effects of recipient cell type from those of donor irradiation dose and to determine the relevance of these responses to primary healthy tissues.
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BibTeX
@article{tudor2026protoninduced,
title = {{Proton-Induced Bystander Signaling Drives Cell-Type-Specific Proteomic Remodeling in Chondrocytes and Endothelial Cells}},
author = {Mihaela Tudor and Benoît Bernay and Mihaela Temelie and Liviu Craciun and François Chevalier and Diana Iulia Savu},
journal = {Cancers},
year = {2026},
month = nov,
doi = {10.3390/cancers18213534},
url = {https://www.mdpi.com/2072-6694/18/21/3534},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Proton-Induced Bystander Signaling Drives Cell-Type-Specific Proteomic Remodeling in Chondrocytes and Endothelial Cells
AU - Mihaela Tudor
AU - Benoît Bernay
AU - Mihaela Temelie
AU - Liviu Craciun
AU - François Chevalier
AU - Diana Iulia Savu
PY - 2026
DA - 2026/11/03
JO - Cancers
DO - 10.3390/cancers18213534
UR - https://www.mdpi.com/2072-6694/18/21/3534
AB - Background/Objectives: Radiation-induced bystander effects (RIBEs), whereby irradiated cells transmit biological signals to neighboring, non-irradiated cells, are a well-recognized phenomenon in radiobiology. However, proton-induced RIBEs remain incompletely understood. This study investigated the bystander responses elicited by proton-irradiated chondrosarcoma cells in non-irradiated chondrocytes and endothelial cells. Methods: T/C-28A2 chondrocytes and EA.hy926 endothelial cells were exposed to conditioned medium (CM) collected from SW1353 chondrosarcoma cells irradiated with protons at doses ranging from 0.1 to 2 Gy. Clonogenic survival and micronucleus (MN) assays were initially performed to assess the susceptibility of recipient cells to bystander signaling. Based on these findings, cell cycle distribution, reactive oxygen species (ROS) level, and proteomic profiles were subsequently analyzed under the most responsive experimental conditions. Results: CM from proton-irradiated chondrosarcoma cells induced significant but cell-type-specific bystander responses. Chondrocytes were most responsive to CM from cells irradiated with 0.1 Gy, exhibiting reduced clonogenic survival, increased micronucleus formation, and adaptive-like proteomic changes consistent with reduced proliferation and extracellular matrix remodeling. In contrast, endothelial cells responded predominantly to conditioned medium from 2 Gy irradiated cells, displaying reduced survival, increased genomic instability, cell cycle perturbations, persistent ROS accumulation, and extensive proteomic remodeling involving elevated levels of proteins associated with metabolism and DNA repair proteins. Network analysis further revealed cell-type-specific alterations in inflammatory, mitochondrial, and intracellular signaling pathways, highlighting distinct mechanisms underlying bystander response. Conclusions: Proton-induced bystander responses differed between the two recipient cell models and were associated with distinct proteomic profiles under the selected experimental conditions. These findings identify candidate proteins and pathways for further investigation but do not establish causal mechanisms or validated biomarkers. Further studies are needed to distinguish the effects of recipient cell type from those of donor irradiation dose and to determine the relevance of these responses to primary healthy tissues.
SN - 2072-6694
ER -