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Anti‐interleukin‐6 receptor antibody prevents muscle atrophy in colon‐26 adenocarcinoma‐bearing mice with modulation of lysosomal and ATP‐ubiquitin‐dependent proteolytic pathways
Author(s) -
Fujita Junya,
Tsujinaka Toshimasa,
Jano Masahiko,
Ebisui Chikara,
Saito Hiroyuki,
Katsume Asao,
Akamatsu Kenichi,
Ohsugi Yoshiyuki,
Shiozaki Hitoshi,
Monden Morito
Publication year - 1996
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/(sici)1097-0215(19961127)68:5<637::aid-ijc14>3.0.co;2-z
Subject(s) - ubiquitin , muscle atrophy , atrophy , pathology , biology , proteolytic enzymes , medicine , immunology , enzyme , biochemistry , gene
Abstract Progression of skeletal muscle atrophy is one of the characteristic features in cancer patients. Interleukin‐6 (IL‐6) has been reported to be responsible for the loss of lean body mass during cancer cachexia in colon‐26 adenocarcinoma (C‐26)‐bearing mice. This study was carried out to elucidate the intracellular proteolytic pathways operating in skeletal muscle in C‐26‐bearing mice, and to examine the effect of anti IL‐6 receptor antibody on muscle atrophy. On day 17 after tumor inoculation, the gastrocnemius muscle weight of C‐26‐bearing mice had significantly decreased to 69% of that of the pair‐fed control mice. This weight loss occurred in association with increases in the mRNA levels of cathepsins B and L, poly‐ubiquitin (Ub) and the subunits of proteasomes in the muscles. Furthermore, enzymatic activity of cathepsin B+L in the muscles also increased to 119% of the control. The administration of antimurine IL‐6 receptor antibody to C‐26‐bearing mice reduced the weight loss of the gastrocnemius muscles to 84% of that of the control mice, whose enzymatic activity of cathepsin B+L and mRNA levels of cathepsin L and poly‐Ub were significantly suppressed compared with those of the C‐26‐bearing mice. Our data indicate that both the lysosomal cathepsin pathway and the ATP‐dependent proteolytic pathway might be involved in the muscle atrophy of C‐26‐bearing mice. The results also suggest that anti IL‐6 receptor antibody could be a potential therapeutic agent against muscle atrophy in cancer cachexia by inhibiting these proteolytic systems. © 1996 Wiley‐Liss, Inc.