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Tumor inoculation site affects the development of cancer cachexia and muscle wasting
Author(s) -
Matsuyama Tatsuzo,
Ishikawa Takeshi,
Okayama Tetsuya,
Oka Kaname,
Adachi Satoko,
Mizushima Katsura,
Kimura Reiko,
Okajima Manabu,
Sakai Hiromi,
Sakamoto Naoyuki,
Katada Kazuhiro,
Kamada Kazuhiro,
Uchiyama Kazuhiko,
Handa Osamu,
Takagi Tomohisa,
Kokura Satoshi,
Naito Yuji,
Itoh Yoshito
Publication year - 2015
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.29620
Subject(s) - cachexia , wasting , endocrinology , adipose tissue , medicine , intraperitoneal injection , tumor microenvironment , tumor necrosis factor alpha , cancer , gastrocnemius muscle , tumor progression , skeletal muscle
The phenotype and severity of cancer cachexia differ among tumor types and metastatic site in individual patients. In this study, we evaluated if differences in tumor microenvironment would affect the development of cancer cachexia in a murine model, and demonstrated that body weight, adipose tissue and gastrocnemius muscle decreased in tumor‐bearing mice. Interestingly, a reduction in heart weight was observed in the intraperitoneal tumor group but not in the subcutaneous group. We evaluated 23 circulating cytokines and members of the TGF‐β family, and found that levels of IL‐6, TNF‐α and activin A increased in both groups of tumor‐bearing mice. Eotaxin and G‐CSF levels in the intraperitoneal tumor group were higher than in the subcutaneous group. Atrogin 1 and MuRF1 mRNA expressions in the gastrocnemius muscle increased significantly in both groups of tumor‐bearing mice, however, in the myocardium, expression of these mRNAs increased in the intraperitoneal group but not in subcutaneous group. Based on these results, we believe that differences in microenvironment where tumor cells develop can affect the progression and phenotype of cancer cachexia through alterations in various circulating factors derived from the tumor microenvironment.