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Am J Clin Nutr. 2013 Dec;98(6):1485-92. doi: 10.3945/ajcn.113.063859. Epub 2013 Oct 9.

Autophagic-lysosomal pathway is the main proteolytic system modified in the skeletal muscle of esophageal cancer patients.

Author information

1
Departments of Anesthesiology and Intensive Care (NT, MK, and OR) and Surgery (LL), Gastrocentrum, Karolinska University Hospital Huddinge and Karolinska Institutet, Stockholm, Sweden, and the Department of Clinical Science, Danderyds Hospital & Department of Surgery, Ersta Hospital, Stockholm, Sweden (AT).

Abstract

BACKGROUND:

In cancer cachexia, muscle depletion is related to morbidity and mortality. Muscle-wasting mechanisms in cancer patients are not fully understood.

OBJECTIVE:

We investigated the involvement of the proteolytic systems (proteasome, autophagic-lysosomal, calpain, and caspase) in muscle wasting during cancer cachexia.

DESIGN:

Esophageal cancer patients [n = 14; mean ± SD age: 64.1 ± 6.6 y] and weight-stable control patients undergoing reflux surgery (n = 8; age: 57.5 ± 5.8 y) were included. Enzymatic activities were measured in the vastus lateralis and diaphragm. Protein expressions were also measured in the vastus lateralis of control (n = 7) and cancer (n = 8) patients.

RESULTS:

Proteasome, calpain, and caspase 3 activities in the vastus lateralis and diaphragm muscles did not differ between the 2 groups. Cathepsin B and L activities were 90% (± SD) [2.4 ± 0.2 compared with 1.3 ± 0.2 pmol 7-amido-4-methylcoumarin (AMC) · μg protein⁻¹ · min⁻¹; P < 0.001] and 115% (5.3 ± 0.4 compared with 2.5 ± 0.3 pmol AMC · μg protein⁻¹ · min⁻¹; P < 0.001) greater, respectively, in the vastus lateralis of cancer patients than in that of control subjects. We observed (in conjunction with increased lysosomal protease activities) higher microtubule-associated protein 1 light chain 3B-II/I ratios (0.14 ± 0.08 compared with 0.04 ± 0.04) and cathepsin B and L expressions in the vastus lateralis of cancer patients than in that of control subjects (P < 0.05). Protein expression of p62 in the vastus lateralis did not differ between the 2 groups.

CONCLUSIONS:

The autophagic-lysosomal pathway in the skeletal muscle of cancer patients was modified, whereas other proteolytic systems were unchanged. These findings suggest involvement of the autophagic-lysosomal proteolytic system during cancer cachexia development in humans.

PMID:
24108784
DOI:
10.3945/ajcn.113.063859
[Indexed for MEDLINE]

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