PEGylated catalase prevents metastatic tumor growth aggravated by tumor removal.

Abstract

Although surgical removal is a primary option for treating tumors, it can lead to the increased growth of metastatic tumors. Because surgical procedures may generate reactive oxygen species (ROS), known promoters of tumor metastasis and growth, we investigated whether PEGylated catalase (PEG-catalase, plasma half-life of 13.6 h) was able to prevent this after surgical removal of a footpad tumor in mice. Murine melanoma cells labeled with the firefly luciferase gene were used to monitor the distribution of tumor cells. After inoculation into the footpad, tumor cells were found in the lung, and the number increased with time. The surgical removal of the footpad tumor significantly (p < 0.05) increased the number of metastatic tumor cells and the level of plasma lipoperoxides. An intravenous injection of PEG-catalase significantly (p < 0.05) suppressed the metastatic tumor growth as well as the peroxidation. Quantitative RT-PCR and Western blot analyses indicated that PEG-catalase markedly reduced the increase in the expression of epidermal growth factor receptor. These findings indicate that the removal of tumor produces ROS, which then aggravate metastatic tumor growth by activating several growth factors. PEG-catalase can effectively prevent this metastatic tumor growth by detoxifying the ROS.

• Authors: Kenji Hyoudou, Makiya Nishikawa, Yuki Kobayashi, Yukari Umeyama, Fumiyoshi Yamashita, Mitsuru Hashida
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 41 Issue 9 Pg. 1449-58 (Nov 01 2006) ISSN: 0891-5849 [Print] United States
• PMID: 17023272 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Oxidants
• Reactive Oxygen Species
• catalase-polyethylene glycol
• Polyethylene Glycols
• Hydrogen Peroxide
• Catalase
• Luciferases

Topics

• Animals
• Blotting, Western
• Catalase (therapeutic use)
• Fireflies (enzymology)
• Hydrogen Peroxide (pharmacology)
• Luciferases (metabolism)
• Lung Neoplasms (enzymology, prevention & control, secondary)
• Male
• Melanoma, Experimental (drug therapy, enzymology, surgery)
• Mice
• Mice, Inbred C57BL
• Oxidants (pharmacology)
• Polyethylene Glycols (therapeutic use)
• Reactive Oxygen Species (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Survival Rate