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

Int J Cancer. 2015 Dec 1;137(11):2558-65. doi: 10.1002/ijc.29620. Epub 2015 Jun 10.

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.

Keywords: cancer cachexia; colorectal cancer; cytokine; muscle wasting; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / blood
  • Animals
  • Cachexia / blood
  • Cachexia / genetics
  • Cachexia / 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
  • Muscular Atrophy / genetics
  • Muscular Atrophy / 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

Substances

  • 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