Discrete roles of cytokines, TNF-α, IL-1, IL-6 in tumor promotion and cell transformation

  • Authors:
    • M. Suganuma
    • S. Okabe
    • M. Kurusu
    • N. Iida
    • S. Ohshima
    • Y. Saeki
    • T. Kishimoto
    • H. Fujiki
  • View Affiliations

  • Published online on: January 1, 2002     https://doi.org/10.3892/ijo.20.1.131
  • Pages: 131-136
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Based on our previous results, which pointed to tumor necrosis factor-α (TNF-α) as the essential cytokine in tumor promotion in mouse skin, we present here three principal findings related to the specific roles of TNF-α, interleukin-1 (IL-1) and IL-6 in tumor promotion (using TNF-α- and IL-6-deficient mice) and in BALB/3T3 cell transformation: i) The previously reported residual tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in TNF-/- mice was confirmed by experiments with TNF+/+ and TNF-/- 129/Svj mice of the same strain, using two-stage carcinogenesis experiments. TPA produced tumors in 100% of TNF+/+ and 78% of TNF-/- mice at 20 weeks, and the average number of tumors per mouse was 11.1 in the former group and 2.1 in the latter. Judging from the expression of various inflammatory cytokine genes in TNF+/+ and TNF-/- mice, the residual tumor promoting activity of TPA in TNF-/- mice may be dependent on expression of IL-1α and IL-1β genes. ii) Tumor promotion by TPA and okadaic acid in IL-6+/+ and IL-6-/- C57/BL6 mice was studied, with TPA producing tumors in 57.1% of IL-6+/+ and 40.0% of IL-6-/- mice at 20 weeks, and okadaic acid in 40.0% of IL-6+/+ and 53.3% of IL-6-/- mice. Thus, there was no significant difference between TPA or okadaic acid tumor promotion in either group. In addition, expression of IL-6 gene in skin of both types of mice suggested that IL-6 is not the essential cytokine in tumor promotion, since it can be replaced by other cytokines. iii) In transformed clones of BALB/3T3 cells induced by TNF-α alone, IL-1α gene expression was induced after transformation by TNF-α had occurred, which did not occur in parental cells. Expression patterns of TNF-α, IL-1β, IL-6 and IL-10, along with TGF-β, were similar in both parental and transformed cells. Considering all these results, we conclude that various cytokines have discrete roles in tumor promotion and cell transformation.

Related Articles

Journal Cover

January 2002
Volume 20 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Suganuma, M., Okabe, S., Kurusu, M., Iida, N., Ohshima, S., Saeki, Y. ... Fujiki, H. (2002). Discrete roles of cytokines, TNF-α, IL-1, IL-6 in tumor promotion and cell transformation. International Journal of Oncology, 20, 131-136. https://doi.org/10.3892/ijo.20.1.131
MLA
Suganuma, M., Okabe, S., Kurusu, M., Iida, N., Ohshima, S., Saeki, Y., Kishimoto, T., Fujiki, H."Discrete roles of cytokines, TNF-α, IL-1, IL-6 in tumor promotion and cell transformation". International Journal of Oncology 20.1 (2002): 131-136.
Chicago
Suganuma, M., Okabe, S., Kurusu, M., Iida, N., Ohshima, S., Saeki, Y., Kishimoto, T., Fujiki, H."Discrete roles of cytokines, TNF-α, IL-1, IL-6 in tumor promotion and cell transformation". International Journal of Oncology 20, no. 1 (2002): 131-136. https://doi.org/10.3892/ijo.20.1.131