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Published on: July 28, 2020
SOD derivatives prevent metastatic tumor growth aggravated by tumor removal
Kenji Hyoudou1, Makiya Nishikawa, Yuki Kobayashi
1Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Abstract:
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.
Insights
Surgical tumor removal can worsen metastasis by increasing reactive oxygen species (ROS). Superoxide dismutase (SOD) derivatives effectively inhibit this ROS-induced tumor growth and improve survival in mice.
Area of Science:
- Oncology
- Biochemistry
- Immunology
Background:
- Surgical tumor removal, while aggressive, can paradoxically promote metastasis.
- Surgical procedures generate reactive oxygen species (ROS), which are implicated in tumor growth and metastasis.
Purpose of the Study:
- To investigate if superoxide dismutase (SOD) derivatives can inhibit micrometastasis growth post-tumor removal.
- To determine the role of ROS in post-surgical tumor metastasis.
Main Methods:
- Murine melanoma cells (B16-BL6) were used to establish spontaneous pulmonary metastasis in mice.
- Footpad tumors were surgically removed, and plasma lipoperoxides and lung tumor cells were quantified.
- Mice received intravenous injections of SOD or pegylated-SOD derivatives.
Main Results:
- Tumor removal significantly increased plasma lipoperoxides and lung metastatic tumor cells.
- SOD and pegylated-SOD administration significantly inhibited peroxidation and metastatic tumor growth.
- Treatment with SOD derivatives extended the survival period of mice.
Conclusions:
- Tumor removal generates ROS, exacerbating the growth of micrometastases.
- SOD derivatives effectively mitigate post-surgical tumor metastasis by detoxifying ROS.
- SOD derivatives represent a potential therapeutic strategy to prevent tumor recurrence and metastasis.
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