Radiation-induced pulmonary injury accelerated pulmonary metastasis in a mouse model of breast cancer

Abstract

Abstract. 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 in situ 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.

Low-dose photon irradiation induces invasiveness through the SDF-1α/CXCR4 pathway in malignant mesothelioma cells

“…Signaling between SDF-1α and CXCR4 contributes to tumor growth, angiogenesis, invasion and metastases in numerous malignancies [ 21 – 23 ]. In addition, irradiation-enhanced invasiveness of non-small lung cancer and breast cancer has been attributed to the SDF-1α/CXCR4 interaction [ 14 , 24 ]. Moreover, the relationship between MPM and the SDF-1α/CXCR4 chemotactic axis has been reported in previous reports [ 25 , 26 ].…”

Breast cancer lung metastasis: Molecular biology and therapeutic implications

“…111 In a study using radiation-treatment mouse models of breast cancer, Gong et al found that pulmonary injury from radiation-treatment induced CXCL12-CXCR4 overexpression, which resulted in increased number of metastatic nodules in the lungs. 112 Recently, the expression of CXCR4 was reported to be higher in TNBC, which has a propensity for lung metastasis. 113 Although how the CXCL12-CXCR4 axis induces lung metastasis remains unclear, some studies suggest that this may be due to increased macrophages and micro vessel density.…”

Longitudinal microcomputed tomography-derived biomarkers for lung metastasis detection in a syngeneic mouse model: added value to bioluminescence imaging

“…[30][31][32][33][34][35] Repeated μCT scanning using our high-resolution 4D protocol for 5 weeks and even up to 12 consecutive weeks did not induce any lung damage in healthy mice. 36 Because the dose rate and dose delivered during our μCT study are both at least an order of magnitude smaller than the dose and rate applied in radiotherapy research, [26][27][28][37][38][39][40] it is unlikely that metastases would be affected. This is supported by the lack of differences in Lewis lung carcinoma tumor volume found 21 days after irradiation with a therapeutic dose of 12 Gy compared with unirradiated tumor-bearing mice.…”