title: Inhibition of experimental hepatic metastasis by targeted delivery of catalase in mice.
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 x 10(5) 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; 35000 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.
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan. makiya@pharm.kyoto-u.ac.jp
authors.forename: Makiya
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Ayumi
authors.initials: A
authors.lastname: Tamada
authors.forename: Kenji
authors.initials: K
authors.lastname: Hyoudou
authors.forename: Yukari
authors.initials: Y
authors.lastname: Umeyama
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kumai
authors.forename: Emi
authors.initials: E
authors.lastname: Ishida
authors.forename: Frantisek
authors.initials: F
authors.lastname: Staud
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yabe
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Takakura
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000818:Animals; D002374:Catalase / Q000008:administration & dosage* / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000473:pathology; D008099:Liver / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control* / Q000556:secondary*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control*
chemical_list: D002374:Catalase; D020782:Matrix Metalloproteinases