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.

[1]  M. Pollycove Radiobiological Basis of Low-Dose Irradiation in Prevention and Therapy of Cancer , 2007, Dose-response : a publication of International Hormesis Society.

[2]  J. Panés,et al.  Anti-inflammatory effects of low-dose radiotherapy in an experimental model of systemic inflammation in mice. , 2006, International journal of radiation oncology, biology, physics.

[3]  S. Kojima [Induction of glutathione and activation of immune functions by low-dose, whole-body irradiation with gamma-rays]. , 2006, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.

[4]  K. Tsuneyama,et al.  Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma. , 2006, Anticancer research.

[5]  H. Tauchi,et al.  Activation of Antioxidative Enzymes Induced by Low-Dose-Rate Whole‐Body γ Irradiation: Adaptive Response in Terms of Initial DNA Damage , 2006, Radiation research.

[6]  J. S. Rao,et al.  Adenovirus-mediated small interfering RNA against matrix metalloproteinase-2 suppresses tumor growth and lung metastasis in mice , 2006, Molecular Cancer Therapeutics.

[7]  S. Kojima,et al.  Suppression of Atopic Dermatitis and Tumor Metastasis in Mice by Small Amounts of Radon , 2006, Radiation research.

[8]  P. Opolon,et al.  Angiogenesis and tumor growth inhibition by a matrix metalloproteinase inhibitor targeting radiation-induced invasion , 2005, Molecular Cancer Therapeutics.

[9]  S. Itohara,et al.  Contribution of host MMP‐2 and MMP‐9 to promote tumor vascularization and invasion of malignant keratinocytes , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[10]  W. Stetler-Stevenson,et al.  Tissue Inhibitors of Metalloproteinase 2 Inhibits Endothelial Cell Migration through Increased Expression of RECK , 2004, Cancer Research.

[11]  L. Chodosh,et al.  Conditional Overexpression of Active Transforming Growth Factor β1 In vivo Accelerates Metastases of Transgenic Mammary Tumors , 2004, Cancer Research.

[12]  Shuji Kojima,et al.  Low Dose γ-Rays Activate Immune Functions via Induction of Glutathione and Delay Tumor Growth , 2004 .

[13]  N. El-Sharkawy,et al.  The potential palliative role and possible immune modulatory effects of low-dose total body irradiation in relapsed or chemo-resistant non-Hodgkin's lymphoma. , 2003, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[14]  Shu-zheng Liu Nonlinear Dose-Response Relationship in the Immune System following Exposure to Ionizing Radiation: Mechanisms and Implications , 2003, Nonlinearity in biology, toxicology, medicine.

[15]  J. Cuttler,et al.  Can Cancer Be Treated with Low Doses of Radiation , 2003 .

[16]  S. Kojima,et al.  Elevation of Glutathione Induced by Low-Dose Gamma Rays and its Involvement in Increased Natural Killer Activity , 2002, Radiation research.

[17]  S. Hattori,et al.  Real-time zymography and reverse zymography: a method for detecting activities of matrix metalloproteinases and their inhibitors using FITC-labeled collagen and casein as substrates. , 2002, Analytical biochemistry.

[18]  Z. Werb,et al.  The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis. , 2001, Trends in cell biology.

[19]  L. Devy,et al.  Down-regulation of vascular endothelial growth factor by tissue inhibitor of metalloproteinase-2: effect on in vivo mammary tumor growth and angiogenesis. , 2001, Cancer research.

[20]  W. Stetler-Stevenson,et al.  Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) Suppresses TKR-Growth Factor Signaling Independent of Metalloproteinase Inhibition* , 2001, The Journal of Biological Chemistry.

[21]  K. Brand,et al.  Treatment of colorectal liver metastases by adenoviral transfer of tissue inhibitor of metalloproteinases-2 into the liver tissue. , 2000, Cancer research.

[22]  Thiennu H. Vu,et al.  Matrix metalloproteinases: effectors of development and normal physiology. , 2000, Genes & development.

[23]  N. Willich,et al.  Dose-dependent induction of transforming growth factor β (TGF-β) in the lung tissue of fibrosis-prone mice after thoracic irradiation , 1999 .

[24]  Y. Hosoi,et al.  FUNDAMENTAL AND CLINICAL STUDIES ON CANCER CONTROL WITH TOTAL OR UPPER HALF BODY IRRADIATION , 1997 .

[25]  P. Basset,et al.  Matrix metalloproteinases as stromal effectors of human carcinoma progression: therapeutic implications. , 1997, Matrix biology : journal of the International Society for Matrix Biology.

[26]  A. Shinagawa,et al.  Cell growth-promoting activity of tissue inhibitor of metalloproteinases-2 (TIMP-2). , 1994, Journal of cell science.

[27]  Y. Hosoi,et al.  Suppressive effect of low dose total body irradiation on lung metastasis: dose dependency and effective period. , 1993, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[28]  W. Stetler-Stevenson,et al.  Tissue inhibitor of metalloproteinase‐2 (TIMP‐2) has erythroid‐potentiating activity , 1992, FEBS letters.