Molecular analysis of the cytokine network involved in cachexia in colon 26 adenocarcinoma-bearing mice

K. Yasumoto, N. Mukaida, A. Harada, K. Kuno, M. Akiyama, E. Nakashima, N. Fujioka, M. Mai, T. Kasahara, K. Fujimoto-Ouchi, K. Mori, Y. Tanaka, K. Matsushima

Research output: Contribution to journalArticle

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Abstract

Two clones, one cachexigenic (clone 20) and the other noncachexigenic (clone 5), from a murine colon adenocarcinoma, colon 26 cells, were used to analyze the involvement of immune reactions as well as the cytokine network in cachexia. Clone 20 induced cachexia in nude and SCID mice as well as in normal BALB/c mice, suggesting that lymphocytes played little, if any, role in the process. Both clones failed to express mRNA of interleukin (IL) 1α, IL-1β, IL-6, and tumor necrosis factor a in vitro with or without the coculture of NIH3T3 cells or spleen cells. However, IL-6 mRNA was selectively detected at the tumor site of clone 20 but not at that of clone 5-bearing mice. In contrast, tumor necrosis factor a mRNA was detected at tumor sites and in spleens of only clone 5-bearing mice, suggesting a potential role of IL-6, but not tumor necrosis factor α, in inducing cachexia. Anti-IL-6 antibody partially reversed the weight loss induced by clone 20, whereas the continuous infusion of IL-6 failed to cause weight loss, despite being associated with an elevation of a serum acute phase protein. These results suggest that IL-6 is necessary but not sufficient for the induction of cachexia. Both clones expressed IL-6 mRNA in the presence of IL-1 in vitro, and mice bearing either clone expressed IL-1β mRNA at the tumor site. Moreover, IL-1 receptor antagonist (IL-1Ra) mRNA was detected at the tumor site of clone 5-bearing mice but not at that of clone 20-bearing mice, suggesting that IL-1Ra might block IL-1 activity to reduce IL-6 production in clone 5-bearing mice. However, the transfection of clone 20 with IL-1Ra cDNA failed to abolish its capacity to produce IL-6 and to cause cachexia. Collectively, additional factor(s) besides IL-1Ra and IL-1β may control IL- 6 and some other cachexigenic factor production, thereby causing cachexia in this model.

Original languageEnglish
Pages (from-to)921-927
Number of pages7
JournalCancer Research
Volume55
Issue number4
Publication statusPublished - 1995
Externally publishedYes

Fingerprint

Cachexia
Colon
Adenocarcinoma
Clone Cells
Cytokines
Interleukin-6
Interleukin-1
Messenger RNA
Tumor Necrosis Factor-alpha
Interleukins
Weight Loss
Neoplasms
Spleen
Interleukin-1 Receptors
SCID Mice
Acute-Phase Proteins
Coculture Techniques
Nude Mice

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Yasumoto, K., Mukaida, N., Harada, A., Kuno, K., Akiyama, M., Nakashima, E., ... Matsushima, K. (1995). Molecular analysis of the cytokine network involved in cachexia in colon 26 adenocarcinoma-bearing mice. Cancer Research, 55(4), 921-927.

Molecular analysis of the cytokine network involved in cachexia in colon 26 adenocarcinoma-bearing mice. / Yasumoto, K.; Mukaida, N.; Harada, A.; Kuno, K.; Akiyama, M.; Nakashima, E.; Fujioka, N.; Mai, M.; Kasahara, T.; Fujimoto-Ouchi, K.; Mori, K.; Tanaka, Y.; Matsushima, K.

In: Cancer Research, Vol. 55, No. 4, 1995, p. 921-927.

Research output: Contribution to journalArticle

Yasumoto, K, Mukaida, N, Harada, A, Kuno, K, Akiyama, M, Nakashima, E, Fujioka, N, Mai, M, Kasahara, T, Fujimoto-Ouchi, K, Mori, K, Tanaka, Y & Matsushima, K 1995, 'Molecular analysis of the cytokine network involved in cachexia in colon 26 adenocarcinoma-bearing mice', Cancer Research, vol. 55, no. 4, pp. 921-927.
Yasumoto K, Mukaida N, Harada A, Kuno K, Akiyama M, Nakashima E et al. Molecular analysis of the cytokine network involved in cachexia in colon 26 adenocarcinoma-bearing mice. Cancer Research. 1995;55(4):921-927.
Yasumoto, K. ; Mukaida, N. ; Harada, A. ; Kuno, K. ; Akiyama, M. ; Nakashima, E. ; Fujioka, N. ; Mai, M. ; Kasahara, T. ; Fujimoto-Ouchi, K. ; Mori, K. ; Tanaka, Y. ; Matsushima, K. / Molecular analysis of the cytokine network involved in cachexia in colon 26 adenocarcinoma-bearing mice. In: Cancer Research. 1995 ; Vol. 55, No. 4. pp. 921-927.
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abstract = "Two clones, one cachexigenic (clone 20) and the other noncachexigenic (clone 5), from a murine colon adenocarcinoma, colon 26 cells, were used to analyze the involvement of immune reactions as well as the cytokine network in cachexia. Clone 20 induced cachexia in nude and SCID mice as well as in normal BALB/c mice, suggesting that lymphocytes played little, if any, role in the process. Both clones failed to express mRNA of interleukin (IL) 1α, IL-1β, IL-6, and tumor necrosis factor a in vitro with or without the coculture of NIH3T3 cells or spleen cells. However, IL-6 mRNA was selectively detected at the tumor site of clone 20 but not at that of clone 5-bearing mice. In contrast, tumor necrosis factor a mRNA was detected at tumor sites and in spleens of only clone 5-bearing mice, suggesting a potential role of IL-6, but not tumor necrosis factor α, in inducing cachexia. Anti-IL-6 antibody partially reversed the weight loss induced by clone 20, whereas the continuous infusion of IL-6 failed to cause weight loss, despite being associated with an elevation of a serum acute phase protein. These results suggest that IL-6 is necessary but not sufficient for the induction of cachexia. Both clones expressed IL-6 mRNA in the presence of IL-1 in vitro, and mice bearing either clone expressed IL-1β mRNA at the tumor site. Moreover, IL-1 receptor antagonist (IL-1Ra) mRNA was detected at the tumor site of clone 5-bearing mice but not at that of clone 20-bearing mice, suggesting that IL-1Ra might block IL-1 activity to reduce IL-6 production in clone 5-bearing mice. However, the transfection of clone 20 with IL-1Ra cDNA failed to abolish its capacity to produce IL-6 and to cause cachexia. Collectively, additional factor(s) besides IL-1Ra and IL-1β may control IL- 6 and some other cachexigenic factor production, thereby causing cachexia in this model.",
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AU - Akiyama, M.

AU - Nakashima, E.

AU - Fujioka, N.

AU - Mai, M.

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AU - Fujimoto-Ouchi, K.

AU - Mori, K.

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