A cytokine signal inhibitor for rheumatoid arthritis enhances cancer metastasis via depletion of NK cells in an experimental lung metastasis mouse model of colon cancer

  • Authors:
    • Hideki Shimaoka
    • Shinsuke Takeno
    • Kenji Maki
    • Takahide Sasaki
    • Suguru Hasegawa
    • Yuichi Yamashita
  • View Affiliations

  • Published online on: June 23, 2017     https://doi.org/10.3892/ol.2017.6473
  • Pages: 3019-3027
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Abstract

Current therapy for rheumatoid arthritis (RA) relies on global suppression of the immune response or specific blockade of inflammatory cytokines. However, it is unclear how immunosuppressants affect patients with cancer. Therefore, in the present study, the effect of three biological agents, tofacitinib, anti‑mouse IL‑6 receptor antibody (MR16‑1) and etanercept, which are used for the treatment of RA diseases, on a tumor‑bearing mouse model was investigated. The effect of the three agents was examined using a mouse lung‑metastasis model with the murine colon 26 cancer cell line. Lymphocyte subsets and natural killer (NK) cells in peripheral blood and spleen were analyzed using fluorescence-activated cell sorting, and the number of lung surface nodules was examined. In the continuous tofacitinib administration (15 mg/kg/day) group, the number of lung surface nodules was significantly increased compared with that of the vehicle‑treated group (vehicle, 1.20±0.58; tofacitinib, 35.6±10.81; P<0.01). NK cell number in the blood and spleen of tofacitinib‑treated mice was decreased 10‑fold, and the percentage of cluster of differentiation (CD)11+CD27‑ NK cells was significantly reduced. MR16‑1 [8 mg/mouse; once a week; intraperitoneal (i.p.)] or etanercept (1 mg/mouse; 3 times a week; i.p.) treatment did not affect the number of NK cells or lung metastasis. In the present study, immunosuppressants that target cytokines, including tofacitinib, were demonstrated to inhibit the proliferation and differentiation of NK cells, and exhibit the potential to promote cancer metastasis using a mouse model of lung metastasis.
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September-2017
Volume 14 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Shimaoka H, Takeno S, Maki K, Sasaki T, Hasegawa S and Yamashita Y: A cytokine signal inhibitor for rheumatoid arthritis enhances cancer metastasis via depletion of NK cells in an experimental lung metastasis mouse model of colon cancer. Oncol Lett 14: 3019-3027, 2017
APA
Shimaoka, H., Takeno, S., Maki, K., Sasaki, T., Hasegawa, S., & Yamashita, Y. (2017). A cytokine signal inhibitor for rheumatoid arthritis enhances cancer metastasis via depletion of NK cells in an experimental lung metastasis mouse model of colon cancer. Oncology Letters, 14, 3019-3027. https://doi.org/10.3892/ol.2017.6473
MLA
Shimaoka, H., Takeno, S., Maki, K., Sasaki, T., Hasegawa, S., Yamashita, Y."A cytokine signal inhibitor for rheumatoid arthritis enhances cancer metastasis via depletion of NK cells in an experimental lung metastasis mouse model of colon cancer". Oncology Letters 14.3 (2017): 3019-3027.
Chicago
Shimaoka, H., Takeno, S., Maki, K., Sasaki, T., Hasegawa, S., Yamashita, Y."A cytokine signal inhibitor for rheumatoid arthritis enhances cancer metastasis via depletion of NK cells in an experimental lung metastasis mouse model of colon cancer". Oncology Letters 14, no. 3 (2017): 3019-3027. https://doi.org/10.3892/ol.2017.6473