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Inhibition of experimental hepatic metastasis by targeted delivery of catalase in mice

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Abstract

Bovine liver catalase derivatives possessing diverse tissue distribution properties were synthesized, and their effects on hepatic metastasis of colon carcinoma cells were examined in mice. An intraportal injection of 1 × 105 colon 26 cells resulted in the formation of more than 50 metastatic colonies on the surface of the liver at 14 days after injection. An intravenous injection of catalase (CAT; 35 000 units/kg of body weight) significantly (P < 0.001) reduced the number of the colonies in the liver. Galactosylated (Gal-), mannosylated (Man-) and succinylated (Suc-) CAT were also tested in the same system. Of these derivatives, Gal-CAT showed the greatest inhibitory effect on hepatic metastasis, and the number of colonies was significantly (P < 0.001) smaller than following treatment with catalase. High activities of matrix metalloproteinases (MMPs), especially MMP-9, were detected in the liver of mice bearing metastatic tumor tissues, which was significantly (P < 0.05) reduced by Gal-CAT. These results, combined with our previous finding that Gal-CAT can be efficiently delivered to hepatocytes, indicate that the targeted delivery of catalase to the liver by galactosylation is a promising approach to suppress hepatic metastasis. Decreased MMP activity by catalase delivery seems to be involved in its anti-metastatic effect.

Abbreviations: CAT – bovine liver catalase; ECM – extracellular matrix; Gal – galactosylated; HBSS – Hanks' balanced salt solution; H2O2– hydrogen peroxide; Man – mannosylated; MMP – matrix metalloproteinase; ROS – reactive oxygen species; Suc – succinylated; SOD – superoxide dismutase

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Authors
  1. Makiya Nishikawa
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  2. Ayumi Tamada
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  3. Kenji Hyoudou
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  4. Yukari Umeyama
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  5. Yuki Takahashi
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  6. Yuki Kobayashi
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  7. Hitomi Kumai
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  8. Emi Ishida
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  9. Frantisek Staud
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  10. Yoshiyuki Yabe
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  11. Yoshinobu Takakura
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  12. Fumiyoshi Yamashita
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Nishikawa, M., Tamada, A., Hyoudou, K. et al. Inhibition of experimental hepatic metastasis by targeted delivery of catalase in mice. Clin Exp Metastasis 21, 213–221 (2004). https://doi.org/10.1023/B:CLIN.0000037706.13747.5e

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