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Ubiquitin‐proteasome pathway and nuclear factor‐κB activity in skeletal muscle of mildly weight‐losing cancer patients
Author(s) -
Langen Ramon C,
Minnaard Ronnie,
Kelders Marco,
Dingemans AnneMarie,
Hesselink Matthijs,
Schols Annemie
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a387-c
Subject(s) - cachexia , skeletal muscle , medicine , endocrinology , tumor necrosis factor alpha , sarcopenia , inflammation , systemic inflammation , muscle atrophy , cancer , lung cancer , cancer research
Non‐small‐cell lung cancer (NSCLC) is often associated with a systemic inflammatory response and loss of muscle mass (cancer cachexia). In experimental cachexia increased proteolysis through the ubiquitin‐proteasome pathway (UPP) is essential for the loss of muscle mass. Tumor necrosis factor α (TNFα) and the transcriptional regulator nuclear factor κB (NF‐κB) have been implicated in skeletal muscle UPP activation. The aim of this study was to investigate whether the UPP was activated in skeletal muscle of NSCLC patients, and whether systemic inflammation in patients correlated with markers of muscle NF‐κB activity. Vastus lateralis muscle biopsies were collected of 12 NSCLC patients (5% weight loss) and 8 control subjects. Chymotrypsin‐ and caspase‐like proteasome activities were not different, whereas atrogin‐1/MAFbx, but not MuRF‐1, mRNA levels were increased in muscle biopsies of NSCLC patients vs. controls. Although muscle IκBα and TNFα mRNA levels were not different between the two groups, strong correlations between IκBα and both, plasma soluble TNF receptor 55 (R=0.74, p=0.01) and C‐reactive protein (R=0.86, p=0.001) were observed in patients only. Taking the very mild weight loss into account, our results suggest that atrogin‐1 may be an early marker of cancer cachexia. In addition, we show evidence for an association between systemic inflammation and muscle NF‐κB activity in NSCLC patients.