Sex differences in the relationship of IL-6 signaling to cancer cachexia progression

Kimbell L. Hetzler, Justin P. Hardee, Melissa J. Puppa, Aditi A. Narsale, Shuichi Sato, J. Mark Davis, James Carson

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

A devastating aspect of cancer cachexia is severe loss of muscle and fat mass. Though cachexia occurs in both sexes, it is not well-defined in the female. The ApcMin/+ mouse is genetically predisposed to develop intestinal tumors; circulating IL-6 is a critical regulator of cancer cachexia in the male ApcMin/+ mouse. The purpose of this study was to examine the relationship between IL-6 signaling and cachexia progression in the female ApcMin/+ mouse. Male and female ApcMin/+ mice were examined during the initiation and progression of cachexia. Another group of females had IL-6 overexpressed between 12 and 14. weeks or 15-18. weeks of age to determine whether IL-6 could induce cachexia. Cachectic female ApcMin/+ mice lost body weight, muscle mass, and fat mass; increased muscle IL-6 mRNA expression was associated with these changes, but circulating IL-6 levels were not. Circulating IL-6 levels did not correlate with downstream signaling in muscle in the female. Muscle IL-6r mRNA expression and SOCS3 mRNA expression as well as muscle IL-6r protein and STAT3 phosphorylation increased with severe cachexia in both sexes. Muscle SOCS3 protein increased in cachectic females but decreased in cachectic males. IL-6 overexpression did not affect cachexia progression in female ApcMin/+ mice. Our results indicate that female ApcMin/+ mice undergo cachexia progression that is at least initially IL-6-independent. Future studies in the female will need to determine mechanisms underlying regulation of IL-6 response and cachexia induction.

Original languageEnglish (US)
Pages (from-to)816-825
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1852
Issue number5
DOIs
StatePublished - May 1 2015
Externally publishedYes

Fingerprint

Cachexia
Sex Characteristics
Interleukin-6
Neoplasms
Muscles
Messenger RNA
Fats
STAT3 Transcription Factor
Muscle Proteins
Body Weight
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology

Cite this

Sex differences in the relationship of IL-6 signaling to cancer cachexia progression. / Hetzler, Kimbell L.; Hardee, Justin P.; Puppa, Melissa J.; Narsale, Aditi A.; Sato, Shuichi; Davis, J. Mark; Carson, James.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1852, No. 5, 01.05.2015, p. 816-825.

Research output: Contribution to journalArticle

Hetzler, Kimbell L. ; Hardee, Justin P. ; Puppa, Melissa J. ; Narsale, Aditi A. ; Sato, Shuichi ; Davis, J. Mark ; Carson, James. / Sex differences in the relationship of IL-6 signaling to cancer cachexia progression. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2015 ; Vol. 1852, No. 5. pp. 816-825.
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