Gong Hong-Yun, Hu Wei-Guo, Hu Qin-Yong, Li Xiang-Pan, Song Qi-Bin
Department of Oncology, Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Oncol Lett. 2015 Dec;10(6):3613-3618. doi: 10.3892/ol.2015.3810. Epub 2015 Oct 16.
The aim of the present study was to investigate the acceleration of pulmonary metastasis due to pulmonary injury caused by radiation treatment in a mouse model of breast cancer, in addition to determining the associated mechanism. The passive metastatic breast cancer model was used in radiation-treated BALB/c mice. In total, 24 mice were randomly separated into two groups, with 12 mice per group, and the groups were treated with or without pulmonary radiation. The survival time and variation of the weights of the lungs, spleen and liver were recorded. Lung metastasis was also evaluated, and chemokine (C-X-C motif) ligand 12 (CXCL12)/chemokine (C-X-C motif) receptor 4 (CXCR4) expression was determined. The results revealed that the group with radiation-induced pulmonary injury exhibited an increased incidence of pulmonary metastasis and shorter survival time compared with the mice without pulmonary radiation. The radiation-treated group possessed an increased number of metastatic nodules in the lungs, but metastasis was not evident in the liver and spleen. The CXCL12/CXCR4 axis was markedly expressed and the expression was significantly increased subsequent to radiation compared with the expression in normal lung tissues. The present study demonstrated that radiation-induced pulmonary injury may accelerate metastatic tumor growth and decrease the overall survival rate of the mice following injection of tumor cells. Tumor localization and growth may have been favored by metastatic conditioning in the lung subsequent to radiotherapy. The CXCL12/CXCR4 axis may affect key elements in the multistep process of metastasis induced by radiation injury.
本研究的目的是在乳腺癌小鼠模型中，除了确定相关机制外，还研究放射治疗引起的肺损伤导致肺转移加速的情况。在接受放射治疗的BALB/c小鼠中使用被动转移乳腺癌模型。总共24只小鼠被随机分为两组，每组12只，分别接受或不接受肺部放射治疗。记录生存时间以及肺、脾和肝脏重量的变化。还评估了肺转移情况，并测定趋化因子（C-X-C基序）配体12（CXCL12）/趋化因子（C-X-C基序）受体4（CXCR4）的表达。结果显示，与未接受肺部放射治疗的小鼠相比，放射诱导肺损伤组的肺转移发生率增加，生存时间缩短。放射治疗组肺部转移结节数量增加，但肝脏和脾脏未出现明显转移。与正常肺组织中的表达相比，CXCL12/CXCR4轴在放射后明显表达且表达显著增加。本研究表明，放射诱导的肺损伤可能会加速转移瘤生长，并降低注射肿瘤细胞后小鼠的总体生存率。放疗后肺内的转移条件可能有利于肿瘤的定位和生长。CXCL12/CXCR4轴可能影响放射损伤诱导的转移多步骤过程中的关键因素。
