Keywords: low dose radiation, whole-body irradiation, B16 melanoma pulmonary metastasis, matrix metalloproteinase-2, MMP-2, tissue inhibitors, TIMP-2, metastasis inhibition, low radiation, gamma rays, tumour metastasis
The novel mechanism of metastasis inhibition by low-dose whole-body irradiation with gamma-rays
The influence of repeated 0.5 Gy whole-body gamma-ray irradiation on tumour metastasis was examined from the standpoint of tumour invasion in the B16 melanoma pulmonary metastasis model in mice. We confirmed that 0.5 Gy whole-body gamma-ray irradiation (four doses over two weeks) significantly suppressed colony formation in the lungs. In the lung tissue 24 h after irradiation, both the level of matrix metalloproteinase-2 (MMP-2) protein and its activity were significantly decreased. We also found that the activity of MMP-9 was significantly decreased in the lungs after the irradiation. Furthermore, both the expression and activity of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) were increased after the irradiation. These results indicate that a decrease of these MMPs and an increase of TIMP-2 would be involved in the suppression of tumour metastasis by repeated 0.5-Gy gamma irradiation.