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Inhibition of adhesion and proliferation of peritoneally disseminated tumor cells by pegylated catalase

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Abstract

Hydrogen peroxide may aggravate the peritoneal dissemination of tumor cells by activating the expression of a variety of genes. In this study, we used pegylated catalase (PEG-catalase) to examine whether prolonged retention of catalase activity within the peritoneal cavity is effective in inhibiting peritoneal dissemination in mouse models. Murine B16-BL6 cells or colon 26 cells labeled with firefly luciferase gene were inoculated intraperitoneally into syngeneic mice. Compared with unmodified catalase, PEG-catalase was retained in the peritoneal cavity for a long period after intraperitoneal injection. A single injection of PEG-catalase just before tumor inoculation significantly reduced the number of the tumor cells at 1 and 7 days. The changes in the expression of molecules involved in the metastasis were evaluated by real time quantitative PCR analysis. Inoculation of the tumor cells increased the expression of intercellular adhesion molecule (ICAM)-1 in the greater omentum, which was inhibited by PEG-catalase. An injection of PEG-catalase at 3 days after tumor inoculation also reduced the number of the tumor cells, suggesting that processes other than the adhesion of tumor cells to peritoneal organs are also inhibited. Daily doses of PEG-catalase significantly prolonged the survival time of tumor-bearing mice. These results indicate that intraperitoneal injection of PEG-catalase inhibits the multiple processes of peritoneal dissemination of tumor cells by scavenging hydrogen peroxide in the peritoneal cavity.

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Abbreviations

PEG-catalase:

polyethyleneglycol-conjugated catalase

H2O2 :

hydrogen peroxide

ROS:

reactive oxygen species

MMP:

matrix metalloproteinase

ICAM-1:

intercellular adhesion molecule-1

VCAM-1:

vascular cell adhesion molecule-1

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

FBS:

fetal bovine serum

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Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, by Health and Labor Sciences Research Grants for Research on Hepatitis and BSE from the Ministry of Health, Labor and Welfare of Japan and by the 21st Century COE Program “Knowledge Information Infrastructure for Genome Science”.

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Authors and Affiliations

  1. Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan

    Kenji Hyoudou, Yuki Kobayashi, Yukari Kuramoto, Fumiyoshi Yamashita & Mitsuru Hashida

  2. Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan

    Makiya Nishikawa

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  1. Kenji Hyoudou
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  2. Makiya Nishikawa
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  3. Yuki Kobayashi
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  4. Yukari Kuramoto
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  5. Fumiyoshi Yamashita
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  6. Mitsuru Hashida
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Correspondence to Makiya Nishikawa.

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Hyoudou, K., Nishikawa, M., Kobayashi, Y. et al. Inhibition of adhesion and proliferation of peritoneally disseminated tumor cells by pegylated catalase. Clin Exp Metastasis 23, 269–278 (2006). https://doi.org/10.1007/s10585-006-9036-8

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  • DOI: https://doi.org/10.1007/s10585-006-9036-8

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