Poster De Conférence Année : 2014

P047: In vitro Engineering of Human 3D Chondrosarcoma: a Preclinical Model Relevant to Hadrontherapy

Résumé

Objective: The ARCHADE project (Advanced Resource Centre for HADrontherapy in Europe) will erect in Caen within few years a resource center of research and development for hadrontherapy with carbon ions and a cancer treatment facility by protontherapy. The benefit of better ballistic and high efficiency of proton and carbon ions for cancer treatment was demonstrated since two decades. However, if the better ballistic of protontherapy is already successfully used worldwide, hadrontherapy with carbon ions stay underused and raise some concerns about likely side effects for patients. Until now, hadronbiology studies have most focused on signaling and repair of DNA damage pathways induced by ionizing radiation under conditions dramatically different of human homeostasis. Thus, this research needs to be broadened as the ranges of radioresistant cancer cells responses to ionizing radiation are still not fully understood. Methods: Since one decade, 3D models are used in radiobiology to approach tissue and tumors microenvironment. However, vascular damages have been show to play an important role in tissue response to radiation exposure. Except for cartilage, which is the only avascular tissue of human body, all 3D models available are develop without vascular compartment and, per se, have key restraint in their use as relevant model for radiobiology. By using patented hyaline collagen matrix, standardized culture conditions, hypoxia and well defined chondrosarcoma cell lines, we developed a pertinent in vitro 3D model for hadronbiology studies of radioresistant tumors. We use a 225 kV X-rays generator as radiation exposure control (from 2 to 10 Gy) and GANIL facility accelerator (carbon, neon and oxygen ions with LET from 30 to 100 keV/lm and a physic dose of 2 Gy) for radiations. Results: We study the impact of carbon ions irradiation of chondrosarcoma cell lines cultivated in 2D and 3D on global survival (clonogenicity, metabolic assays), genetic stability and oxidative stress. Results show that 2D chondrosarcoma cell lines are 3 time more resistant to X-rays (D10% ¼ 6.6 Gy) that carbon ions (D10% ¼ 2 Gy). However, 3D models cell survival does not show such difference. Furthermore, both 2D chondrosar-coma cell lines and 3D models present a transient H2aX phosphorylation (3 to 6 hours)after 2 Gy exposure of X-rays while the phosphorylation stay high until a least 4 days after the same dose of ions irradiation. Conclusion: The data displayed in this poster show that chondrosarcoma cell lines 3D culture, which restore cell natural micro-environment, strongly change cell fate after ionizing radiations exposure even at high LET. Thus, it may explain some discrepancies between radiobiology studies and clinical data.

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Dates et versions

hal-05459846 , version 1 (15-01-2026)

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  • HAL Id : hal-05459846 , version 1

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Yannick Saintigny, Dounia Hamdi, François Chevalier, Yvonne de Jong, Judith Bovee, et al.. P047: In vitro Engineering of Human 3D Chondrosarcoma: a Preclinical Model Relevant to Hadrontherapy. 53rd Annual Meeting for the Particle Therapy Cooperative Group, Jun 2014, Shanghai (Chine), China. ⟨hal-05459846⟩
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