Yamauchi Yoshikane, Safi Seyer, Orschiedt Lena, Gardyan Adriane, Brons Stephan, Rieber Juliane, Nicolay Nils H, Huber Peter E, Eichhorn Martin, Dienemann Hendrik, Herth Felix J F, Weber Klaus-Josef, Debus Jürgen, Hoffmann Hans, Rieken Stefan
Department of Thoracic Surgery, Thorax Clinic, Heidelberg University, Heidelberg, Germany.
Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany.
Oncotarget. 2017 Jul 10;8(40):68001-68011. doi: 10.18632/oncotarget.19134. eCollection 2017 Sep 15.
Low-dose photon irradiation has repeatedly been suspected to increase a risk of promoting local recurrence of disease or even systemic dissemination. The purpose of this study was to investigate the motility of malignant pleural mesothelioma (MPM) cell lines after low-doses of photon irradiation and to elucidate the mechanism of the detected phenotype.
H28 and H226 MPM cells were examined in clonogenic survival experiments and migration assays with and without various doses of photon and carbon ion irradiation. C-X-C chemokine receptor type 4 (CXCR4), SDF-1α, β integrin, α integrin, and α integrin expressions were analyzed by quantitative FACS analysis, ELISA and western blots. Apoptosis was assessed via Annexin-V-staining.
The migration of MPM cells was stimulated by both fetal bovine serum and by stromal cell-derived factor 1α (SDF-1α). Low doses of photon irradiation (1 Gy and 2 Gy) suppressed clonogenicity, but promoted migration of both H28 and H226 cells through the SDF-1α/CXCR4 pathway. Hypermigration was inhibited by the administration of CXCR4 antagonist, AMD3100. In contrast, corresponding doses of carbon ion irradiation (0.3 Gy and 1 Gy) suppressed clonogenicity, but did not promote MPM cell migration.
Our findings suggest that the co-administration of photon irradiation and the CXCR4-antagonist AMD3100 or the use of carbon ions instead of photons may be possible solutions to reduce the risk of locoregional tumor recurrence after radiotherapy for MPM.
低剂量光子辐射一直被怀疑会增加疾病局部复发甚至全身扩散的风险。本研究的目的是研究低剂量光子辐射后恶性胸膜间皮瘤（MPM）细胞系的迁移能力，并阐明所检测到的表型的机制。
在有或无各种剂量的光子和碳离子辐射的情况下，对H28和H226 MPM细胞进行克隆存活实验和迁移测定。通过定量FACS分析、ELISA和western印迹分析C-X-C趋化因子受体4（CXCR4）、SDF-1α、β整合素、α整合素和α整合素的表达。通过膜联蛋白-V染色评估细胞凋亡。
胎牛血清和基质细胞衍生因子1α（SDF-1α）均刺激MPM细胞的迁移。低剂量的光子辐射（1 Gy和2 Gy）抑制克隆形成能力，但通过SDF-1α/CXCR4途径促进H28和H226细胞的迁移。CXCR4拮抗剂AMD3100的给药抑制了过度迁移。相反，相应剂量的碳离子辐射（0.3 Gy和1 Gy）抑制克隆形成能力，但不促进MPM细胞迁移。
我们的研究结果表明，联合使用光子辐射和CXCR4拮抗剂AMD3100或使用碳离子代替光子可能是降低MPM放疗后局部肿瘤复发风险的可行解决方案。
