Tumor inoculation site affects the development of cancer cachexia and muscle wasting.

Abstract

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.

• Authors: Tatsuzo Matsuyama, Takeshi Ishikawa, Tetsuya Okayama, Kaname Oka, Satoko Adachi, Katsura Mizushima, Reiko Kimura, Manabu Okajima, Hiromi Sakai, Naoyuki Sakamoto, Kazuhiro Katada, Kazuhiro Kamada, Kazuhiko Uchiyama, Osamu Handa, Tomohisa Takagi, Satoshi Kokura, Yuji Naito, Yoshito Itoh
• Journal: International journal of cancer (Int J Cancer) Vol. 137 Issue 11 Pg. 2558-65 (Dec 01 2015) ISSN: 1097-0215 [Electronic] United States
• PMID: 26016447 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 UICC.

Chemical References

• Interleukin-6
• Muscle Proteins
• RNA, Messenger
• Transforming Growth Factor beta
• Tripartite Motif Proteins
• Tumor Necrosis Factor-alpha
• activin A
• Activins
• Fbxo32 protein, mouse
• SKP Cullin F-Box Protein Ligases
• Trim63 protein, mouse
• Ubiquitin-Protein Ligases

Topics

• Activins (blood)
• Animals
• Cachexia (blood, genetics, pathology)
• Cell Line, Tumor
• Disease Models, Animal
• Interleukin-6 (blood)
• Male
• Mice
• Mice, Inbred BALB C
• Muscle Proteins (genetics)
• Muscle, Skeletal (pathology)
• Muscular Atrophy (blood, genetics, pathology)
• Myocardium (pathology)
• RNA, Messenger (genetics)
• SKP Cullin F-Box Protein Ligases (genetics)
• Transforming Growth Factor beta (blood)
• Tripartite Motif Proteins
• Tumor Microenvironment (genetics)
• Tumor Necrosis Factor-alpha (blood)
• Ubiquitin-Protein Ligases (genetics)