Heterogeneity of chondrosarcomas response to irradiations with X-rays and carbon ions: A comparative study on five cell lines

Journal of Bone Oncology

卷:22

Karim Boumédiene¹  Nicolas Girard²  Eva Lhuissier²  Olivier Cauvard²  Marion Lente²  Catherine Baugé²  Martine Boittin²  Juliette Aury-Landas² 

[1] Corresponding author: EA7451 BioConnecT, Université de Caen Normandie, 14032 Caen, France.;

[2] Normandie Univ., Unicaen, EA 7451 Bioconnect, Caen, France;

关键词: Chondrosarcoma;    Resistance;    Genetics;    Radiotherapy;    Apoptosis;    Hypoxia;   

DOI  :  

来源: DOAJ

【 摘 要 】

Objectives: Chondrosarcomas are malignant bone tumors considered as resistant to radiotherapy. To unravel mechanisms of resistance, we compared biological responses of several chondrosarcomas to X-ray irradiations in normoxia and hypoxia. Since hadrontherapy with Carbon-ions gave interesting clinical outcomes, we also investigated this treatment in vitro. Methods: Five human chondrosarcoma cell lines were used and cultured in normoxia or hypoxia. Their sensitivities to irradiations were determined by carrying out survival curves. DNA damage was monitored by γH2AX expression. Apoptosis was assessed by cell cycle analysis and Apo2.7 expression, and by evaluating PARP cleavage. Senescence was evaluated using SA β-galactosidase assay. Necrosis, and autophagy, were evaluated by RIP1 and beclin-1 expression, respectively. Mutations in relevant biological pathways were screened by whole-exome sequencing. Results: X-ray radiations induced death in some chondrosarcomas by both apoptosis and senescence (CH2879), or by either of them (SW1353 and JJ012), whereas no death was observed in other cell lines (FS090 and 105KC). Molecularly, p21 was overexpressed when senescence was elicited. Genetic analysis allowed to identify putative genes (such as TBX3, CDK2A, HMGA2) permitting to predict cell response to irradiations. Unexpectedly, chronic hypoxia did not favor radioresistance in chondrosarcomas, and even increased the radiosensitivity of JJ012 line. Finally, we show that carbon ions triggered more DNA damages and death than X-rays. Conclusions: Chondrosarcomas have different response to irradiation, possibly due to their strong genetic heterogeneity. p21 expression is suggested as predictive of X-ray-induced senescence. Surprisingly, hypoxia does not increase the radioresistance of chondrosarcomas, but as expected Carbon ion beams are more effective that X-rays in normoxia, whereas their efficiency was also variable depending on cell lines.

【 授权许可】

Unknown