title: 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.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tatsuzo
authors.initials: T
authors.lastname: Matsuyama
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.|Department of Cancer ImmunoCell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.|Department of Cancer ImmunoCell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Okayama
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Oka
authors.affiliation: Department of Cancer ImmunoCell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Adachi
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Katsura
authors.initials: K
authors.lastname: Mizushima
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kimura
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Okajima
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katada
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kamada
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Uchiyama
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Handa
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.|Faculty of Health Medicine, Kyoto Gakuen University, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokura
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
mesh_terms: D028341:Activins / Q000097:blood; D000818:Animals; D002100:Cachexia / Q000097:blood / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000473:pathology*; D009133:Muscular Atrophy / Q000097:blood / Q000235:genetics / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000097:blood; D000070584:Tripartite Motif Proteins; D059016:Tumor Microenvironment / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D015850:Interleukin-6; D009124:Muscle Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000070584:Tripartite Motif Proteins; D014409:Tumor Necrosis Factor-alpha; C422405:activin A; D028341:Activins; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: cancer cachexia; colorectal cancer; cytokine; muscle wasting; tumor microenvironment