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Article

Enhancement of active MMP release and invasive activity of lymph node metastatic tongue cancer cells by elevated signaling via the TNF-α-TNFR1-NF-κB pathway and a possible involvement of angiopoietin-like 4 in lung metastasis

  • Authors:
    • Takuya Tanaka
    • Takahisa Imamura
    • Masakazu Yoneda
    • Atsushi Irie
    • Hidenao Ogi
    • Masashi Nagata
    • Ryoji Yoshida
    • Daiki Fukuma
    • Kenta Kawahara
    • Masanori Shinohara
    • Hideki Nakayama
  • View Affiliations / Copyright

    Affiliations: Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan, Department of Molecular Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan, Department of Immunogenetics, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
  • Pages: 1377-1384
    |
    Published online on: August 10, 2016
       https://doi.org/10.3892/ijo.2016.3653
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Abstract

To study the role of TNF-α in tongue cancer metastasis, we made highly metastatic cells from a human oral squamous cell carcinoma cell line (SAS) by repeating the passage in which the cells were injected into a nude mouse tongue and harvested from metastasized cervical lymph nodes. Cancer cells after 5 passages (GSAS/N5) increased invasive activity 7-fold in a TNF-α receptor 1 (TNFR1)-dependent manner and enhanced mRNA expression of TNF-α and TNFR1. In the highly metastatic cells, NF-κB activation was upregulated via elevated phosphorylation of Akt and Ikkα/β in the signaling pathway and secretion of TNF-α, active MMP-2 and MMP-9 increased. Suppression of increase of TNF-α mRNA expression and MMP secretion by NF-κB inhibitor NBD peptide suggested a positive feedback loop in GSAS/N5 cells; TNF-α activates NF-κB and activated NF-κB induces further TNF-α secretion, leading to increase of active MMP release and promotion of invasion and metastasis of the cells. GSAS/N5 cells that had been injected into the nude mouse tongue and harvested from metastasized lungs multiplied angiopoietin-like 4 (angptl4) expression with enhanced migration activity, which indicated a possible involvement of angptl4 in lung metastasis of the cells. These results suggest that TNF-α and angptl4 promote metastasis of the oral cancer cells, thus, these molecules may be therapeutic targets for patients with tongue cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Tanaka T, Imamura T, Yoneda M, Irie A, Ogi H, Nagata M, Yoshida R, Fukuma D, Kawahara K, Shinohara M, Shinohara M, et al: Enhancement of active MMP release and invasive activity of lymph node metastatic tongue cancer cells by elevated signaling via the TNF-α-TNFR1-NF-κB pathway and a possible involvement of angiopoietin-like 4 in lung metastasis. Int J Oncol 49: 1377-1384, 2016.
APA
Tanaka, T., Imamura, T., Yoneda, M., Irie, A., Ogi, H., Nagata, M. ... Nakayama, H. (2016). Enhancement of active MMP release and invasive activity of lymph node metastatic tongue cancer cells by elevated signaling via the TNF-α-TNFR1-NF-κB pathway and a possible involvement of angiopoietin-like 4 in lung metastasis. International Journal of Oncology, 49, 1377-1384. https://doi.org/10.3892/ijo.2016.3653
MLA
Tanaka, T., Imamura, T., Yoneda, M., Irie, A., Ogi, H., Nagata, M., Yoshida, R., Fukuma, D., Kawahara, K., Shinohara, M., Nakayama, H."Enhancement of active MMP release and invasive activity of lymph node metastatic tongue cancer cells by elevated signaling via the TNF-α-TNFR1-NF-κB pathway and a possible involvement of angiopoietin-like 4 in lung metastasis". International Journal of Oncology 49.4 (2016): 1377-1384.
Chicago
Tanaka, T., Imamura, T., Yoneda, M., Irie, A., Ogi, H., Nagata, M., Yoshida, R., Fukuma, D., Kawahara, K., Shinohara, M., Nakayama, H."Enhancement of active MMP release and invasive activity of lymph node metastatic tongue cancer cells by elevated signaling via the TNF-α-TNFR1-NF-κB pathway and a possible involvement of angiopoietin-like 4 in lung metastasis". International Journal of Oncology 49, no. 4 (2016): 1377-1384. https://doi.org/10.3892/ijo.2016.3653
Copy and paste a formatted citation
x
Spandidos Publications style
Tanaka T, Imamura T, Yoneda M, Irie A, Ogi H, Nagata M, Yoshida R, Fukuma D, Kawahara K, Shinohara M, Shinohara M, et al: Enhancement of active MMP release and invasive activity of lymph node metastatic tongue cancer cells by elevated signaling via the TNF-α-TNFR1-NF-κB pathway and a possible involvement of angiopoietin-like 4 in lung metastasis. Int J Oncol 49: 1377-1384, 2016.
APA
Tanaka, T., Imamura, T., Yoneda, M., Irie, A., Ogi, H., Nagata, M. ... Nakayama, H. (2016). Enhancement of active MMP release and invasive activity of lymph node metastatic tongue cancer cells by elevated signaling via the TNF-α-TNFR1-NF-κB pathway and a possible involvement of angiopoietin-like 4 in lung metastasis. International Journal of Oncology, 49, 1377-1384. https://doi.org/10.3892/ijo.2016.3653
MLA
Tanaka, T., Imamura, T., Yoneda, M., Irie, A., Ogi, H., Nagata, M., Yoshida, R., Fukuma, D., Kawahara, K., Shinohara, M., Nakayama, H."Enhancement of active MMP release and invasive activity of lymph node metastatic tongue cancer cells by elevated signaling via the TNF-α-TNFR1-NF-κB pathway and a possible involvement of angiopoietin-like 4 in lung metastasis". International Journal of Oncology 49.4 (2016): 1377-1384.
Chicago
Tanaka, T., Imamura, T., Yoneda, M., Irie, A., Ogi, H., Nagata, M., Yoshida, R., Fukuma, D., Kawahara, K., Shinohara, M., Nakayama, H."Enhancement of active MMP release and invasive activity of lymph node metastatic tongue cancer cells by elevated signaling via the TNF-α-TNFR1-NF-κB pathway and a possible involvement of angiopoietin-like 4 in lung metastasis". International Journal of Oncology 49, no. 4 (2016): 1377-1384. https://doi.org/10.3892/ijo.2016.3653
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