Label-Free Direct Mass Spectrometry Analysis of the Bystander Effects Induced in Chondrocytes by Chondrosarcoma Cells Irradiated with X-rays and Carbon Ions

Gilbert, Antoine; Payet, Valentin; Bernay, Benoı̂t; Chartier-Garcia, Elisabeth; Testard, Isabelle; Candéias, Serge M.; Chevalier, François

doi:10.31083/j.fbl2709277

Cited by 2 publications

(2 citation statements)

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“…Proteomic analysis of the bystander effects induced in chondrocytes by chondrosarcoma cells exposed to X-rays and C-ions at 100 mGy revealed about 20 proteins that are involved in oxidative stress responses (mitochondria), cellular motility, and exosomes pathways [347]. The conditioned medium contained 40 modified proteins.…”

Section: Ldir Adaptive Responsesmentioning

confidence: 99%

“…In recent years, furthermore, stress granules have become a topic in cancer research [353]. They are involved in various tumor-associated signaling pathways, including cell proliferation, apoptosis, invasion and metastasis, chemotherapy resistance, radiotherapy resistance, immune escape, and bystander effects [354], and this, also, at low doses [347]. Interestingly, in HNSCC cells, ceramide-enriched membrane domains contributed to targeted and nontargeted effects of radiation through modulation of PI3K/AKT signaling [355].…”

Section: Immune and Anti-tumor Ldir Effectsmentioning

confidence: 99%

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Low-Dose Non-Targeted Effects and Mitochondrial Control

Averbeck

2023

IJMS

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Non-targeted effects (NTE) have been generally regarded as a low-dose ionizing radiation (IR) phenomenon. Recently, regarding long distant abscopal effects have also been observed at high doses of IR) relevant to antitumor radiation therapy. IR is inducing NTE involving intracellular and extracellular signaling, which may lead to short-ranging bystander effects and distant long-ranging extracellular signaling abscopal effects. Internal and “spontaneous” cellular stress is mostly due to metabolic oxidative stress involving mitochondrial energy production (ATP) through oxidative phosphorylation and/or anaerobic pathways accompanied by the leakage of O2− and other radicals from mitochondria during normal or increased cellular energy requirements or to mitochondrial dysfunction. Among external stressors, ionizing radiation (IR) has been shown to very rapidly perturb mitochondrial functions, leading to increased energy supply demands and to ROS/NOS production. Depending on the dose, this affects all types of cell constituents, including DNA, RNA, amino acids, proteins, and membranes, perturbing normal inner cell organization and function, and forcing cells to reorganize the intracellular metabolism and the network of organelles. The reorganization implies intracellular cytoplasmic-nuclear shuttling of important proteins, activation of autophagy, and mitophagy, as well as induction of cell cycle arrest, DNA repair, apoptosis, and senescence. It also includes reprogramming of mitochondrial metabolism as well as genetic and epigenetic control of the expression of genes and proteins in order to ensure cell and tissue survival. At low doses of IR, directly irradiated cells may already exert non-targeted effects (NTE) involving the release of molecular mediators, such as radicals, cytokines, DNA fragments, small RNAs, and proteins (sometimes in the form of extracellular vehicles or exosomes), which can induce damage of unirradiated neighboring bystander or distant (abscopal) cells as well as immune responses. Such non-targeted effects (NTE) are contributing to low-dose phenomena, such as hormesis, adaptive responses, low-dose hypersensitivity, and genomic instability, and they are also promoting suppression and/or activation of immune cells. All of these are parts of the main defense systems of cells and tissues, including IR-induced innate and adaptive immune responses. The present review is focused on the prominent role of mitochondria in these processes, which are determinants of cell survival and anti-tumor RT.

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Section: Ldir Adaptive Responsesmentioning

confidence: 99%

Section: Immune and Anti-tumor Ldir Effectsmentioning

confidence: 99%

Low-Dose Non-Targeted Effects and Mitochondrial Control

Averbeck

2023

IJMS

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Pilot screening of potential matrikines resulting from collagen breakages through ionizing radiation

Montanari,

Schwob,

Marie-Brasset

et al. 2024

Radiat Environ Biophys

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Little is known regarding radiation-induced matrikines and the possible degradation of extracellular matrix following therapeutic irradiation. The goal of this study was to determine if irradiation can cut collagen proteins at specific sites, inducing potentially biologically active peptides against cartilage cells. Chondrocytes cultured as 3D models were evaluated for extracellular matrix production. Bystander molecules were analyzed in vitro in the conditioned medium of X-irradiated chondrocytes. Preferential breakage sites were analyzed in collagen polypeptide by mass spectrometry and resulting peptides were tested against chondrocytes. 3D models of chondrocytes displayed a light extracellular matrix able to maintain the structure. Irradiated and bystander chondrocytes showed a surprising radiation sensitivity at low doses, characteristic of the presence of bystander factors, particularly following 0.1 Gy. The glycine-proline peptidic bond was observed as a preferential cleavage site and a possible weakness of the collagen polypeptide after irradiation. From the 46 collagen peptides analyzed against chondrocytes culture, 20 peptides induced a reduction of viability and 5 peptides induced an increase of viability at the highest concentration between 0.1 and 1 µg/ml. We conclude that irradiation promoted a site-specific degradation of collagen. The potentially resulting peptides induce negative or positive regulations of chondrocyte growth. Taken together, these results suggest that ionizing radiation causes a degradation of cartilage proteins, leading to a functional unbalance of cartilage homeostasis after exposure, contributing to cartilage dysfunction.

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Label-Free Direct Mass Spectrometry Analysis of the Bystander Effects Induced in Chondrocytes by Chondrosarcoma Cells Irradiated with X-rays and Carbon Ions

Cited by 2 publications

References 46 publications

Low-Dose Non-Targeted Effects and Mitochondrial Control

Low-Dose Non-Targeted Effects and Mitochondrial Control

Pilot screening of potential matrikines resulting from collagen breakages through ionizing radiation

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