Open Access

IL-23 promotes growth and proliferation in human squamous cell carcinoma of the oral cavity

  • Authors:
    • Masakatsu Fukuda
    • Masahiro Ehara
    • Seiji Suzuki
    • Yoshihiro Ohmori
    • Hideaki Sakashita
  • View Affiliations

  • Published online on: June 1, 2010     https://doi.org/10.3892/ijo_00000620
  • Pages: 1355-1365
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Abstract

Interleukin (IL)-23 is a heterodimeric cytokine, comprising IL-12p40 and the cloned IL-23-specific p19 subunit, was identified as a cancer-associated cytokine in a recent study. Like IL-12, IL-23 is expressed predominantly by activated dendritic cells and phagocytic cells. These cytokines antagonistically regulate local inflammatory responses in the tumor microenvironment and infiltration by intraepithelial lymphocytes. We have previously demonstrated the expression of IL-23 and its receptors in human oral squamous cell carcinoma (HOSCC) cell lines and tissue. Hence, this study investigated whether IL-23 has a role in the growth and proliferation of oral cancer cells by examining the expression kinetics of IL-23 and NF-κB activity, in vitro and in vivo. IL-23, which constitutively expressed in oral cancer, was enhanced by TNF-α and IL-23. IL-23 promotes cell proliferation in oral cancer and enhances the transport of nuclear factor-κB (NF-κB p65, RelA) to the nucleus in HSC-3 cells. Furthermore, luciferase reporter assay showed that IL-23 strongly induces RelA activity, and confirmed this finding by knockdown of IL-23 using RNA interference. Although RelA activity was down-regulated by anti-human IL-23p19 polyclonal antibody, used to neutralize the activity of IL-23, apoptosis was not induced. Immunohistochemistry revealed a weak IL-23 immunoreactivity in the cytoplasm of inflammatory infiltrating cells and in the cancer cells derived from 14 of 40 cases (35%) of oral SCC. In contrast, strong RelA immunoreactivity was observed in 30 of 40 cases of SCC (75%), especially consistent with IL-23 positive cells in SCC tissues. These data suggest that IL-23 up-regulates the growth and cell proliferation of oral cancer by promoting the nuclear transactivation of RelA.

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June 2010
Volume 36 Issue 6

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

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Spandidos Publications style
Fukuda M, Ehara M, Suzuki S, Ohmori Y and Sakashita H: IL-23 promotes growth and proliferation in human squamous cell carcinoma of the oral cavity. Int J Oncol 36: 1355-1365, 2010.
APA
Fukuda, M., Ehara, M., Suzuki, S., Ohmori, Y., & Sakashita, H. (2010). IL-23 promotes growth and proliferation in human squamous cell carcinoma of the oral cavity. International Journal of Oncology, 36, 1355-1365. https://doi.org/10.3892/ijo_00000620
MLA
Fukuda, M., Ehara, M., Suzuki, S., Ohmori, Y., Sakashita, H."IL-23 promotes growth and proliferation in human squamous cell carcinoma of the oral cavity". International Journal of Oncology 36.6 (2010): 1355-1365.
Chicago
Fukuda, M., Ehara, M., Suzuki, S., Ohmori, Y., Sakashita, H."IL-23 promotes growth and proliferation in human squamous cell carcinoma of the oral cavity". International Journal of Oncology 36, no. 6 (2010): 1355-1365. https://doi.org/10.3892/ijo_00000620