SOD derivatives prevent metastatic tumor growth aggravated by tumor removal.
Although surgical removal is the most aggressive strategy to treat removable tumors, it sometimes aggravates tumor growth in metastatic sites. Because surgical procedures generate reactive oxygen species (ROS), known promoters of tumor metastasis and growth, we examined whether the growth of micrometastasis is inhibited by superoxide dismutase (SOD) derivatives after surgical removal of tumors in mice. Murine melanoma B16-BL6 cells were inoculated into the footpad to establish spontaneous pulmonary metastasis. The removal of the footpad tumor significantly (P < 0.05) increased the level of plasma lipoperoxides and the number of tumor cells in the lung. An intravenous injection of SOD or its pegylated-SOD derivative significantly (P < 0.05) inhibited the peroxidation and metastatic tumor growth. It also extended the survival period of mice undergoing removal of the footpad tumor. These findings indicate that the removal of tumor produces ROS, which then aggravates the growth of tumor cells in micrometastases. SOD derivatives can effectively prevent this metastatic tumor growth by detoxifying ROS.
Hyoudou
Kenji
K
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Nishikawa
Makiya
M
Kobayashi
Yuki
Y
Ikemura
Mai
M
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000818:Animals; D008054:Lipid Peroxides / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000517:prevention & control* / Q000556:secondary*; D008297:Male; D008546:Melanoma, Experimental / Q000097:blood / Q000556:secondary* / Q000601:surgery*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000627:therapeutic use*
D008054:Lipid Peroxides; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase