Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 Apr;67(4):680–685. doi: 10.1038/bjc.1993.126

Increased protein degradation and decreased protein synthesis in skeletal muscle during cancer cachexia.

K L Smith 1, M J Tisdale 1
PMCID: PMC1968351  PMID: 8471425

Abstract

The effects of progressive cachexia on protein metabolism in skeletal muscle has been investigated in mice bearing the MAC16 adenocarcinoma which produces cachexia with tumour burdens of < 1% of the host weight. Weight loss was accompanied by loss of whole body nitrogen in proportion to the overall loss of body mass. Using L-[4-3H]phenylalanine to label proteins in gastrocnemius muscle, a significant depression (60%) in protein synthesis occurred in animals with a weight loss between 15 and 30% accompanied by an increase in protein degradation, which increased with increasing weight loss between 15 and 30%. Muscle degradation in vitro could be achieved by serum from cachectic animals, which appeared to contain a proteolysis-inducing factor. These results suggest that the increased degradation of skeletal muscle seen in this model of cachexia may be due to a circulating proteolysis-inducing factor.

Full text

PDF
683

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baracos V. E., Goldberg A. L. Maintenance of normal length improves protein balance and energy status in isolated rat skeletal muscles. Am J Physiol. 1986 Oct;251(4 Pt 1):C588–C596. doi: 10.1152/ajpcell.1986.251.4.C588. [DOI] [PubMed] [Google Scholar]
  2. Beck S. A., Tisdale M. J. Nitrogen excretion in cancer cachexia and its modification by a high fat diet in mice. Cancer Res. 1989 Jul 15;49(14):3800–3804. [PubMed] [Google Scholar]
  3. Beck S. A., Tisdale M. J. Production of lipolytic and proteolytic factors by a murine tumor-producing cachexia in the host. Cancer Res. 1987 Nov 15;47(22):5919–5923. [PubMed] [Google Scholar]
  4. Belizario J. E., Katz M., Chenker E., Raw I. Bioactivity of skeletal muscle proteolysis-inducing factors in the plasma proteins from cancer patients with weight loss. Br J Cancer. 1991 May;63(5):705–710. doi: 10.1038/bjc.1991.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bibby M. C., Double J. A., Ali S. A., Fearon K. C., Brennan R. A., Tisdale M. J. Characterization of a transplantable adenocarcinoma of the mouse colon producing cachexia in recipient animals. J Natl Cancer Inst. 1987 Mar;78(3):539–546. [PubMed] [Google Scholar]
  6. Carrascosa J. M., Martínez P., Núez de Castro I. Nitrogen movement between host and tumor in mice inoculated with Ehrlich ascitic tumor cells. Cancer Res. 1984 Sep;44(9):3831–3835. [PubMed] [Google Scholar]
  7. Clark C. M., Goodlad G. A. Depletion of proteins of phasic and tonic muscles in tumour-bearing rats. Eur J Cancer. 1971 Feb;7(1):3–9. doi: 10.1016/0014-2964(71)90088-0. [DOI] [PubMed] [Google Scholar]
  8. Emery P. W., Edwards R. H., Rennie M. J., Souhami R. L., Halliday D. Protein synthesis in muscle measured in vivo in cachectic patients with cancer. Br Med J (Clin Res Ed) 1984 Sep 8;289(6445):584–586. doi: 10.1136/bmj.289.6445.584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Flores E. A., Bistrian B. R., Pomposelli J. J., Dinarello C. A., Blackburn G. L., Istfan N. W. Infusion of tumor necrosis factor/cachectin promotes muscle catabolism in the rat. A synergistic effect with interleukin 1. J Clin Invest. 1989 May;83(5):1614–1622. doi: 10.1172/JCI114059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hellerstein M. K., Meydani S. N., Meydani M., Wu K., Dinarello C. A. Interleukin-1-induced anorexia in the rat. Influence of prostaglandins. J Clin Invest. 1989 Jul;84(1):228–235. doi: 10.1172/JCI114145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lundholm K., Bylund A. C., Holm J., Scherstén T. Skeletal muscle metabolism in patients with malignant tumor. Eur J Cancer. 1976 Jun;12(6):465–473. doi: 10.1016/0014-2964(76)90036-0. [DOI] [PubMed] [Google Scholar]
  12. Norton J. A., Shamberger R., Stein T. P., Milne G. W., Brennan M. F. The influence of tumor-bearing on protein metabolism in the rat. J Surg Res. 1981 May;30(5):456–462. doi: 10.1016/0022-4804(81)90090-1. [DOI] [PubMed] [Google Scholar]
  13. O'Keefe S. J., Ogden J., Ramjee G., Rund J. Contribution of elevated protein turnover and anorexia to cachexia in patients with hepatocellular carcinoma. Cancer Res. 1990 Feb 15;50(4):1226–1230. [PubMed] [Google Scholar]
  14. Rodemann H. P., Goldberg A. L. Arachidonic acid, prostaglandin E2 and F2 alpha influence rates of protein turnover in skeletal and cardiac muscle. J Biol Chem. 1982 Feb 25;257(4):1632–1638. [PubMed] [Google Scholar]
  15. Rotman E. I., Brostrom M. A., Brostrom C. O. Inhibition of protein synthesis in intact mammalian cells by arachidonic acid. Biochem J. 1992 Mar 1;282(Pt 2):487–494. doi: 10.1042/bj2820487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Shaw J. H., Humberstone D. A., Douglas R. G., Koea J. Leucine kinetics in patients with benign disease, non-weight-losing cancer, and cancer cachexia: studies at the whole-body and tissue level and the response to nutritional support. Surgery. 1991 Jan;109(1):37–50. [PubMed] [Google Scholar]
  17. Strelkov A. B., Fields A. L., Baracos V. E. Effects of systemic inhibition of prostaglandin production on protein metabolism in tumor-bearing rats. Am J Physiol. 1989 Aug;257(2 Pt 1):C261–C269. doi: 10.1152/ajpcell.1989.257.2.C261. [DOI] [PubMed] [Google Scholar]
  18. Tessitore L., Bonelli G., Baccino F. M. Early development of protein metabolic perturbations in the liver and skeletal muscle of tumour-bearing rats. A model system for cancer cachexia. Biochem J. 1987 Jan 1;241(1):153–159. doi: 10.1042/bj2410153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. WAALKES T. P., UDENFRIEND S. A fluorometric method for the estimation of tyrosine in plasma and tissues. J Lab Clin Med. 1957 Nov;50(5):733–736. [PubMed] [Google Scholar]
  20. Wu G. Y., Thompson J. R. The effect of ketone bodies on alanine and glutamine metabolism in isolated skeletal muscle from the fasted chick. Biochem J. 1988 Oct 1;255(1):139–144. doi: 10.1042/bj2550139. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES