Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Feb;79(5-6):764–769. doi: 10.1038/sj.bjc.6690123

Tumour inoculation site-dependent induction of cachexia in mice bearing colon 26 carcinoma

T Matsumoto* 1,1, K Fujimoto-Ouchi 1, S Tamura 1, Y Tanaka 1, H Ishitsuka 1
PMCID: PMC2362659  PMID: 10070867

Abstract

Murine colon 26 carcinoma growing at either subcutaneous (s.c.) or intramuscular (i.m.) inoculation sites causes cachexia in mice. Such animals show extensive loss of body weight, wasting of the muscle and adipose tissues, hypoglycaemia, and hypercalcaemia, even when the tumour weight comprises only about 1.9% of carcass weight. In contrast, the same tumour when inoculated into the liver does not cause any sign of tumour-related cachexia even when the tumour becomes much larger (6.6% of carcass weight). Interleukin 6 (IL-6), a mediator associated with cachexia in this tumour model, is detected at high levels both in the tumour tissues and in the circulating blood of mice bearing colon 26 tumour at the s.c. inoculation site. In contrast, only minute levels of IL-6 are detected in the tumour grown in the liver. The colon 26 tumour grown in the liver does not lose its ability to cause cachexia, because the tumour when re-inoculated s.c. is able to cause extensive weight loss and produce IL-6 as did the original colon 26 cell line. Histological studies revealed differences in the composition of tumour tissues: the tumours grown in the subcutis consist of many polygonal tumour cells, extended-intercellular space, and high vascular density, whereas those grown in the liver consist of spindle-shaped tumour cells. Thus, the environment where tumour cells grow would be a critical factor in determining the cachectic phenotype of cancer cells, including their ability to produce IL-6. 1999 Cancer Research Campaign

Keywords: colon 26, cachexia, IL-6, inoculation site, malignancy

Full Text

The Full Text of this article is available as a PDF (453.0 KB).

Selected References

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

  1. Arend W. P., Joslin F. G., Massoni R. J. Effects of immune complexes on production by human monocytes of interleukin 1 or an interleukin 1 inhibitor. J Immunol. 1985 Jun;134(6):3868–3875. [PubMed] [Google Scholar]
  2. Eda H., Tanaka Y., Ishitsuka H. 5'-Deoxy-5-fluorouridine improves cachexia by a mechanism independent of its antiproliferative action in colon 26 adenocarcinoma-bearing mice. Cancer Chemother Pharmacol. 1991;29(1):1–6. doi: 10.1007/BF00686327. [DOI] [PubMed] [Google Scholar]
  3. Fiers W. Tumor necrosis factor. Characterization at the molecular, cellular and in vivo level. FEBS Lett. 1991 Jul 22;285(2):199–212. doi: 10.1016/0014-5793(91)80803-b. [DOI] [PubMed] [Google Scholar]
  4. Fujimoto-Ouchi K., Tamura S., Mori K., Tanaka Y., Ishitsuka H. Establishment and characterization of cachexia-inducing and -non-inducing clones of murine colon 26 carcinoma. Int J Cancer. 1995 May 16;61(4):522–528. doi: 10.1002/ijc.2910610416. [DOI] [PubMed] [Google Scholar]
  5. Gelin J., Moldawer L. L., Lönnroth C., Sherry B., Chizzonite R., Lundholm K. 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):415–421. [PubMed] [Google Scholar]
  6. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  7. Matthys P., Dijkmans R., Proost P., Van Damme J., Heremans H., Sobis H., Billiau A. Severe cachexia in mice inoculated with interferon-gamma-producing tumor cells. Int J Cancer. 1991 Aug 19;49(1):77–82. doi: 10.1002/ijc.2910490115. [DOI] [PubMed] [Google Scholar]
  8. Matthys P., Heremans H., Opdenakker G., Billiau A. Anti-interferon-gamma antibody treatment, growth of Lewis lung tumours in mice and tumour-associated cachexia. Eur J Cancer. 1991;27(2):182–187. doi: 10.1016/0277-5379(91)90483-t. [DOI] [PubMed] [Google Scholar]
  9. Moldawer L. L., Georgieff M., Lundholm K. Interleukin 1, tumour necrosis factor-alpha (cachectin) and the pathogenesis of cancer cachexia. Clin Physiol. 1987 Aug;7(4):263–274. doi: 10.1111/j.1475-097x.1987.tb00169.x. [DOI] [PubMed] [Google Scholar]
  10. Mori M., Yamaguchi K., Honda S., Nagasaki K., Ueda M., Abe O., Abe K. Cancer cachexia syndrome developed in nude mice bearing melanoma cells producing leukemia-inhibitory factor. Cancer Res. 1991 Dec 15;51(24):6656–6659. [PubMed] [Google Scholar]
  11. Nakajima M., Morikawa K., Fabra A., Bucana C. D., Fidler I. J. Influence of organ environment on extracellular matrix degradative activity and metastasis of human colon carcinoma cells. J Natl Cancer Inst. 1990 Dec 19;82(24):1890–1898. doi: 10.1093/jnci/82.24.1890. [DOI] [PubMed] [Google Scholar]
  12. Oliff A., Defeo-Jones D., Boyer M., Martinez D., Kiefer D., Vuocolo G., Wolfe A., Socher S. H. Tumors secreting human TNF/cachectin induce cachexia in mice. Cell. 1987 Aug 14;50(4):555–563. doi: 10.1016/0092-8674(87)90028-6. [DOI] [PubMed] [Google Scholar]
  13. Steinkasserer A., Estaller C., Weiss E. H., Sim R. B. Human interleukin-1 receptor antagonist is expressed in liver. FEBS Lett. 1992 Sep 21;310(1):60–62. doi: 10.1016/0014-5793(92)81146-d. [DOI] [PubMed] [Google Scholar]
  14. Stovroff M. C., Fraker D. L., Swedenborg J. A., Norton J. A. Cachectin/tumor necrosis factor: a possible mediator of cancer anorexia in the rat. Cancer Res. 1988 Aug 15;48(16):4567–4572. [PubMed] [Google Scholar]
  15. Strassmann G., Fong M., Kenney J. S., Jacob C. O. Evidence for the involvement of interleukin 6 in experimental cancer cachexia. J Clin Invest. 1992 May;89(5):1681–1684. doi: 10.1172/JCI115767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Strassmann G., Jacob C. O., Evans R., Beall D., Fong M. Mechanisms of experimental cancer cachexia. Interaction between mononuclear phagocytes and colon-26 carcinoma and its relevance to IL-6-mediated cancer cachexia. J Immunol. 1992 Jun 1;148(11):3674–3678. [PubMed] [Google Scholar]
  17. Strassmann G., Masui Y., Chizzonite R., Fong M. Mechanisms of experimental cancer cachexia. Local involvement of IL-1 in colon-26 tumor. J Immunol. 1993 Mar 15;150(6):2341–2345. [PubMed] [Google Scholar]
  18. Tamura S., Ouchi K. F., Mori K., Endo M., Matsumoto T., Eda H., Tanaka Y., Ishitsuka H., Tokita H., Yamaguchi K. Involvement of human interleukin 6 in experimental cachexia induced by a human uterine cervical carcinoma xenograft. Clin Cancer Res. 1995 Nov;1(11):1353–1358. [PubMed] [Google Scholar]
  19. Tanaka Y., Eda H., Tanaka T., Udagawa T., Ishikawa T., Horii I., Ishitsuka H., Kataoka T., Taguchi T. Experimental cancer cachexia induced by transplantable colon 26 adenocarcinoma in mice. Cancer Res. 1990 Apr 15;50(8):2290–2295. [PubMed] [Google Scholar]
  20. Tracey K. J., Wei H., Manogue K. R., Fong Y., Hesse D. G., Nguyen H. T., Kuo G. C., Beutler B., Cotran R. S., Cerami A. Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. J Exp Med. 1988 Mar 1;167(3):1211–1227. doi: 10.1084/jem.167.3.1211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Vidal-Vanaclocha F., Glaves D., Barbera-Guillem E., Weiss L. Quantitative microscopy of mouse colon 26 cells growing in different metastatic sites. Br J Cancer. 1991 May;63(5):748–752. doi: 10.1038/bjc.1991.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Yoneda T., Alsina M. A., Chavez J. B., Bonewald L., Nishimura R., Mundy G. R. Evidence that tumor necrosis factor plays a pathogenetic role in the paraneoplastic syndromes of cachexia, hypercalcemia, and leukocytosis in a human tumor in nude mice. J Clin Invest. 1991 Mar;87(3):977–985. doi: 10.1172/JCI115106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Yoneda T., Nakai M., Moriyama K., Scott L., Ida N., Kunitomo T., Mundy G. R. Neutralizing antibodies to human interleukin 6 reverse hypercalcemia associated with a human squamous carcinoma. Cancer Res. 1993 Feb 15;53(4):737–740. [PubMed] [Google Scholar]

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

RESOURCES