Skeletal muscle mRNA levels for cathepsin B, but not components of the ubiquitin-proteasome pathway, are increased in patients with lung cancer referred for thoracotomy.
Muscle wasting is a common and prominent feature of advanced cancer, including lung cancer. Evidence from animal experiments suggests that accelerated proteolysis via the ubiquitin--proteasome pathway is the primary cause of cancer-related cachexia. However, there are few data on the role of this pathway in determining muscle wasting in human cancer. The present study was designed to measure whether skeletal muscle gene expression of components of the ubiquitin-proteasome pathway and/or the lysosomal proteolytic pathway was increased in patients with early lung cancer. A total of 36 patients with lung cancer referred for curative resection and 10 control subjects had biopsies of latissimus dorsi muscle taken at operation. mRNA levels of four components of the ubiquitin-proteasome pathway, i.e. polyubiquitin, C2 alpha proteasome subunit, 14 kDa ubiquitin-carrier protein and ubiquitin-activating protein, and of two lysosomal proteolytic enzymes, i.e. cathepsin B and cathepsin D, were measured using quantitative Northern blotting. mRNA levels for cathepsin B, but not for components of the ubiquitin--proteasome pathway, were higher in patients with cancer compared with controls (P=0.01). Among lung cancer patients, cathepsin B mRNA levels correlated with fat-free mass index (r = -0.57, P=0.003) and tumour stage (r(s)=0.45, P=0.03), and were higher in smokers (P=0.04). Thus gene expression of the lysosomal protease cathepsin B is increased in the skeletal muscle of patients with early lung cancer, and the strong inverse relationship with fat-free mass suggests that cathepsin B may have a role in inducing muscle wasting in the early stages of lung cancer.
Jagoe
R Thomas
RT
Department of Medicine, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK. tjagoe@hotmail.com
Redfern
Christopher P F
CP
Roberts
Russell G
RG
Gibson
G John
GJ
Goodship
Timothy H J
TH
D000368:Aged; D000704:Analysis of Variance; D015152:Blotting, Northern; D002100:Cachexia / Q000378:metabolism*; D016022:Case-Control Studies; D002401:Cathepsin B / Q000235:genetics*; D002402:Cathepsin D / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D008025:Ligases / Q000235:genetics; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics; D018482:Muscle, Skeletal / Q000737:chemistry*; D009367:Neoplasm Staging; D009752:Nutritional Status; D025821:Polyubiquitin / Q000235:genetics; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000032:analysis*; D012907:Smoking; D044763:Ubiquitin-Conjugating Enzymes
D009097:Multienzyme Complexes; D012333:RNA, Messenger; C046288:ubiquitin carrier proteins; D025821:Polyubiquitin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D044763:Ubiquitin-Conjugating Enzymes; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D002402:Cathepsin D; D046988:Proteasome Endopeptidase Complex; D008025:Ligases