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Inhibition of experimental pulmonary metastasis by controlling biodistribution of catalase in mice
Author(s) -
Nishikawa Makiya,
Tamada Ayumi,
Kumai Hitomi,
Yamashita Fumiyoshi,
Hashida Mitsuru
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10387
Subject(s) - catalase , metastasis , enzyme , lung , chemistry , biodistribution , saline , pharmacology , pathology , endocrinology , medicine , biology , biochemistry , cancer , in vitro
In a previous study, we showed that targeted delivery of bovine liver catalase to hepatocytes by direct galactosylation augmented the inhibitory effect of the enzyme on experimental hepatic metastasis of colon carcinoma cells (unpublished data). Here, we examined the ability of catalase to inhibit tumor metastasis to the lung by controlling its biodistribution. Four types of catalase derivative, Gal‐CAT, Man‐CAT, Suc‐CAT and PEG‐CAT, were synthesized. Experimental pulmonary metastasis was induced in mice by i.v. injection of 1 × 10 5 colon 26 tumor cells. An i.v. injection of catalase (35,000 units/kg) partially, but significantly, decreased the number of colonies in the lung 2 weeks after tumor injection, from 93 ± 29 (saline injection) to 63 ± 23 ( p < 0.01). Suc‐CAT, Man‐CAT and Gal‐CAT showed effects similar to those of catalase on the number of colonies. However, PEG‐CAT greatly inhibited pulmonary metastasis to 22 ± 11 ( p < 0.001). Furthermore, s.c. injection of catalase also greatly inhibited metastasis (11 ± 6, p < 0.001). Neither inactivated catalase nor BSA showed any effects on the number of metastatic colonies, indicating that the enzymatic activity of catalase to detoxify H 2 O 2 is the critical factor inhibiting metastasis. 111 In‐PEG‐CAT showed a sustained concentration in plasma, whereas s.c.‐injected 111 In‐catalase was slowly absorbed from the injection site. These results suggest that retention of catalase activity in the circulation is a promising approach to inhibit pulmonary metastasis. © 2002 Wiley‐Liss, Inc.