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PMID: 8254032 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Tumor necrosis factor-alpha mediates changes in tissue protein turnover in a rat cancer cachexia model.

The Journal of clinical investigation ·Vol. 92 ·No. 6 ·1993-12-00 ·Pages 2783-9

Costelli P, Carbó N, Tessitore L, Bagby GJ, Lopez-Soriano FJ, Argilés JM, Baccino FM

Abstract

Rats bearing the Yoshida AH-130 ascites hepatoma showed enhanced fractional rates of protein degradation in gastrocnemius muscle, heart, and liver, while fractional synthesis rates were similar to those in non-tumor bearing rats. This hypercatabolic pattern was associated with marked perturbations of the hormonal homeostasis and presence of tumor necrosis factor in the circulation. The daily administration of a goat anti-murine TNF IgG to tumor-bearing rats decreased protein degradation rates in skeletal muscle, heart, and liver as compared with tumor-bearing rats receiving a nonimmune goat IgG. The anti-TNF treatment was also effective in attenuating early perturbations in insulin and corticosterone homeostasis. Although these results suggest that tumor necrosis factor plays a significant role in mediating the changes in protein turnover and hormone levels elicited by tumor growth, the inability of such treatment to prevent a reduction in body weight implies that other mediators or tumor-related events were also involved.

MeSH Terms
Animals Cachexia/metabolism Immunoglobulin G/pharmacology Kidney/metabolism Liver/metabolism Liver Neoplasms/metabolism,physiopathology Liver Neoplasms, Experimental/metabolism,physiopathology Male Muscles/metabolism Myocardium/metabolism Organ Specificity Proteins/metabolism Rats Rats, Wistar Reference Values Tumor Necrosis Factor-alpha/immunology,physiology
Chemicals
Immunoglobulin G Proteins Tumor Necrosis Factor-alpha
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Costelli P
Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, Italy.
Carbó N
Tessitore L
Bagby G J
Lopez-Soriano F J
Argilés J M
Baccino F M
References (43)
43 references, click to expand
  1. Induction of weight loss and metabolic alterations by human recombinant tumour necrosis factor.
    Br J Cancer. 1988 Sep;58(3):345-9 PMID: 3179188
  2. Protein measurement with the Folin phenol reagent.
    J Biol Chem. 1951 Nov;193(1):265-75 PMID: 14907713
  3. Inhibition of basal protein degradation in rat embryo fibroblasts by cycloheximide: correlation with activities of lysosomal proteases.
    J Cell Physiol. 1978 Dec;97(3 Pt 1):267-83 PMID: 730770
  4. Cancer cachexia.
    Cancer. 1979 May;43(5 Suppl):2004-12 PMID: 376104
  5. Cancer cachexia in man: a review.
    Invest Cell Pathol. 1979 Jul-Sep;2(3):181-93 PMID: 391780
  6. A comparison of methods for the measurement of protein turnover in vivo.
    Biochem J. 1979 Nov 15;184(2):473-6 PMID: 534542
  7. A rapid and convenient technique for measuring the rate of protein synthesis in tissues by injection of [3H]phenylalanine.
    Biochem J. 1980 Nov 15;192(2):719-23 PMID: 6786283
  8. Control of cell protein catabolism in rat liver. Effects of starvation and administration of cycloheximide.
    Biochem J. 1982 Aug 15;206(2):395-405 PMID: 7150250
  9. Metabolic approaches to cancer cachexia.
    Annu Rev Nutr. 1982;2:277-301 PMID: 6821191
  10. Comparison of in vitro cell cytotoxic assays for tumor necrosis factor.
    J Immunol Methods. 1984 Mar 30;68(1-2):167-75 PMID: 6707477
  11. Cachectin and tumour necrosis factor as two sides of the same biological coin.
    Nature. 1986 Apr 17-23;320(6063):584-8 PMID: 3010124
  12. Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression.
    J Clin Invest. 1986 Nov;78(5):1349-54 PMID: 2429991
  13. Tumour necrosis factor. Polypeptide mediator network.
    Nature. 1987 Mar 26-Apr 1;326(6111):330-1 PMID: 3494200
  14. 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):153-9 PMID: 3566707
  15. Tumors secreting human TNF/cachectin induce cachexia in mice.
    Cell. 1987 Aug 14;50(4):555-63 PMID: 3607879
  16. The acute metabolic effects of tumor necrosis factor administration in humans.
    Arch Surg. 1987 Dec;122(12):1396-400 PMID: 3689116
  17. Interleukin 1 and tumor necrosis factor do not regulate protein balance in skeletal muscle.
    Am J Physiol. 1987 Dec;253(6 Pt 1):C766-73 PMID: 3501247
  18. Tumour necrosis factor in man: clinical and biological observations.
    Br J Cancer. 1987 Dec;56(6):803-8 PMID: 3435706
  19. Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation.
    J Exp Med. 1988 Mar 1;167(3):1211-27 PMID: 3351436
  20. Role of biochemical mediators in clinical nutrition and surgical metabolism.
    JPEN J Parenter Enteral Nutr. 1988 Mar-Apr;12(2):212-8 PMID: 3283388
  21. Activation of protein breakdown and prostaglandin E2 production in rat skeletal muscle in fever is signaled by a macrophage product distinct from interleukin 1 or other known monokines.
    J Clin Invest. 1988 May;81(5):1378-83 PMID: 3284911
  22. Tumor necrosis factor can induce fever in rats without activating protein breakdown in muscle or lipolysis in adipose tissue.
    J Clin Invest. 1988 May;81(5):1384-9 PMID: 3163348
  23. Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins.
    Am J Physiol. 1989 Mar;256(3 Pt 2):R659-65 PMID: 2784290
  24. Effect of recombinant human tumour necrosis factor alpha on protein synthesis in liver, skeletal muscle and skin of rats.
    Biochem J. 1989 Mar 1;258(2):493-7 PMID: 2468333
  25. 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):1614-22 PMID: 2785120
  26. Anticachectin/tumor necrosis factor-alpha antibodies attenuate development of cachexia in tumor models.
    FASEB J. 1989 Jun;3(8):1956-62 PMID: 2721856
  27. Comparative effects of tumour necrosis factor-alpha (cachectin), interleukin-1-beta and tumour growth on amino acid metabolism in the rat in vivo. Absorption and tissue uptake of alpha-amino[1-14C]isobutyrate.
    Biochem J. 1989 Jul 15;261(2):357-62 PMID: 2789041
  28. Metabolic effects of tumour necrosis factor-alpha (cachectin) and interleukin-1.
    Clin Sci (Lond). 1989 Oct;77(4):357-64 PMID: 2680232
  29. Are the catabolic effects of tumor necrosis factor mediated by glucocorticoids?
    Arch Surg. 1990 Jan;125(1):42-7; discussion 47-8 PMID: 2153019
  30. Impact of tolerance on antitumor efficacy of tumor necrosis factor in mice.
    Cancer Res. 1990 Apr 15;50(8):2261-7 PMID: 2317813
  31. Prolonged survival of tumor-bearing rats with repetitive low-dose recombinant tumor necrosis factor.
    Cancer Res. 1990 Jul 1;50(13):3928-33 PMID: 2354441
  32. Cachectic effects of recombinant human tumor necrosis factor in rats.
    Cancer Res. 1990 Jul 1;50(13):4008-13 PMID: 2354450
  33. Interaction between corticosterone and tumor necrosis factor stimulated protein breakdown in rat skeletal muscle, similar to sepsis.
    Surgery. 1990 Aug;108(2):460-6 PMID: 2382237
  34. Divergent efficacy of antibody to tumor necrosis factor-alpha in intravascular and peritonitis models of sepsis.
    J Infect Dis. 1991 Jan;163(1):83-8 PMID: 1984480
  35. Role of endogenous tumor necrosis factor alpha and interleukin 1 for experimental tumor growth and the development of cancer cachexia.
    Cancer Res. 1991 Jan 1;51(1):415-21 PMID: 1703040
  36. Newly identified factors that alter host metabolism in cancer cachexia.
    Trends Pharmacol Sci. 1990 Dec;11(12):473-5 PMID: 2080549
  37. Anti-interferon-gamma antibody treatment, growth of Lewis lung tumours in mice and tumour-associated cachexia.
    Eur J Cancer. 1991;27(2):182-7 PMID: 1827286
  38. Severe cachexia in mice inoculated with interferon-gamma-producing tumor cells.
    Int J Cancer. 1991 Aug 19;49(1):77-82 PMID: 1908442
  39. Anticachectic and antitumor effect of eicosapentaenoic acid and its effect on protein turnover.
    Cancer Res. 1991 Nov 15;51(22):6089-93 PMID: 1657378
  40. Cancer cachexia syndrome developed in nude mice bearing melanoma cells producing leukemia-inhibitory factor.
    Cancer Res. 1991 Dec 15;51(24):6656-9 PMID: 1742740
  41. The role of cytokines in muscle wasting: its relation with cancer cachexia.
    Med Res Rev. 1992 Nov;12(6):637-52 PMID: 1435017
  42. Humoral mediation for cachexia in tumour-bearing rats.
    Br J Cancer. 1993 Jan;67(1):15-23 PMID: 8427775
  43. Measurement of protein turnover in rat liver with (14C)carbonate. Protein turnover during liver regeneration.
    J Biol Chem. 1974 Nov 10;249(21):6836-41 PMID: 4425223
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI116897
Published
1993-12-00
Pages
2783-9
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC288478
Subset
IM
Grants
NIGMS NIH HHS · GM32654 · United States
External Links
PubMed source DOI: 10.1172/JCI116897 PMC Full Text View journal details
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