Skeletal muscle glycoprotein 130's role in Lewis lung carcinoma-induced cachexia

Melissa J. Puppa, Song Gao, Aditi A. Narsale, James Carson

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Chronic inflammation is associated with cachexia-induced skeletal muscle mass loss in cancer. Levels of IL-6 cytokine family members are increased during cancer-related cachexia and induce intracellular signaling through glycoprotein130 (gp130). Although muscle STAT3 and circulating IL-6 are implicated in cancer-induced muscle wasting, there is limited understanding of muscle gp130's role in this process. Therefore, we investigated the role of skeletal muscle gp130 (skm-gp130) in cancer-induced alterations in the regulation of muscle protein turnover. Lewis lung carcinoma (LLC) cells were injected into 8-wk-old skmgp130- knockout (KO) mice or wild-type mice. Skeletal muscle loss was attenuated by 16% in gp130-KO mice, which coincided with attenuated LLC-induced phosphorylation of muscle STAT3, p38, and FOXO3. gp130 KO did not restore mTOR inhibition or alter AMPactivated protein kinase (AMPK) expression. The induction of atrogin expression and p38 phosphorylation in C2C12 myotubes exposed to LLC-treated medium was attenuated by gp130 inhibition, but mTOR inhibition was not restored. STAT signaling inhibition in LLC-treated myotubes did not attenuate the induction of p38 or AMPK phosphorylation. We concluded that, during LLC-induced cachexia, skm-gp130 regulates muscle mass signaling through STAT3 and p38 for the activation of FOXO3 and atrogin, but does not directly regulate the suppression of mTOR.

Original languageEnglish (US)
Pages (from-to)998-1009
Number of pages12
JournalFASEB Journal
Volume28
Issue number2
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Lewis Lung Carcinoma
Cachexia
Muscle
Glycoproteins
Skeletal Muscle
Muscles
Skeletal Muscle Fibers
Phosphorylation
Knockout Mice
Protein Kinases
Interleukin-6
Muscle Neoplasms
Neoplasms
Muscle Proteins
Cytokines
Inflammation
Inhibition (Psychology)
Chemical activation
Cells

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Skeletal muscle glycoprotein 130's role in Lewis lung carcinoma-induced cachexia. / Puppa, Melissa J.; Gao, Song; Narsale, Aditi A.; Carson, James.

In: FASEB Journal, Vol. 28, No. 2, 01.01.2014, p. 998-1009.

Research output: Contribution to journalArticle

Puppa, Melissa J. ; Gao, Song ; Narsale, Aditi A. ; Carson, James. / Skeletal muscle glycoprotein 130's role in Lewis lung carcinoma-induced cachexia. In: FASEB Journal. 2014 ; Vol. 28, No. 2. pp. 998-1009.
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