In vitro engineering of human 3D chondrosarcoma: a preclinical model relevant for investigations of radiation quality impact

BMC Cancer

Research Article

Philippe Galera¹  Magali Demoor¹  Florence Legendre¹  Yannick Saintigny²  Dounia Houria Hamdi²  François Chevalier²  Jean-Louis Lefaix²  Sofia Barbieri³  Jean-Emmanuel Groetz⁴ 

[1] EA4652-Normandie Université, Caen, France;LARIA-IRCM-DSV-Commissariat à l’Energie Atomique et aux Energies Alternatives, CIMAP, GANIL, Bd Henri Becquerel, BP 55027, 14076, Caen, cedex 05, France;LARIA-IRCM-DSV-Commissariat à l’Energie Atomique et aux Energies Alternatives, CIMAP, GANIL, Bd Henri Becquerel, BP 55027, 14076, Caen, cedex 05, France;Università degli Studi di Pavia, Pavia, Italy;UMR6249-Université de Franche-Comté, Besançon, France;

关键词: SW1353 Cell;    Articular Chondrocytes;    Linear Energy Transfer;    Relative Biological Effectiveness;    Collagen Scaffold;   

DOI  :  10.1186/s12885-015-1590-5

 received in 2015-01-06, accepted in 2015-07-31,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe benefit of better ballistic and higher efficiency of carbon ions for cancer treatment (hadron-therapy) is asserted since decades, especially for unresectable or resistant tumors like sarcomas. However, hadron-therapy with carbon ions stays underused and raises some concerns about potential side effects for patients. Chondrosarcoma is a cartilaginous tumor, chemo- and radiation-resistant, that lacks reference models for basic and pre-clinical studies in radiation-biology. Most studies about cellular effects of ionizing radiation, including hadrons, were performed under growth conditions dramatically different from human homeostasis. Tridimensional in vitro models are a fair alternative to animal models to approach tissue and tumors microenvironment.MethodsBy using a collagen matrix, standardized culture conditions, physiological oxygen tension and a well defined chondrosarcoma cell line, we developed a pertinent in vitro 3D model for hadron-biology studies. Low- and high-Linear Energy Transfer (LET) ionizing radiations from GANIL facilities of ~1 keV/μm and 103 ± 4 keV/μm were used respectively, at 2 Gy single dose. The impact of radiation quality on chondrosarcoma cells cultivated in 3D was analyzed on cell death, cell proliferation and DNA repair.ResultsA fair distribution of chondrosarcoma cells was observed in the whole 3D scaffold. Moreover, LET distribution in depth, for ions, was calculated and found acceptable for radiation-biology studies using this kind of scaffold. No difference in cell toxicity was observed between low- and high-LET radiations but a higher rate of proliferation was displayed following high-LET irradiation. Furthermore, 3D models presented a higher and longer induction of H2AX phosphorylation after 2 Gy of high-LET compared to low-LET radiations.ConclusionsThe presented results show the feasibility and usefulness of our 3D chondrosarcoma model in the study of the impact of radiation quality on cell fate. The observed changes in our tissue-like model after ionizing radiation exposure may explain some discrepancies between radiation-biology studies and clinical data.

【 授权许可】

CC BY   
© Hamdi et al. 2015