Open Access

Involvement of the nuclear factor-κB signaling pathway in the regulation of CXC chemokine receptor-4 expression in neuroblastoma cells induced by tumor necrosis factor-α

  • Authors:
    • Yunlai Zhi
    • Hongting Lu
    • Yuhe Duan
    • Weisheng Sun
    • Ge Guan
    • Qian Dong
    • Chuanmin Yang
  • View Affiliations

  • Published online on: December 10, 2014     https://doi.org/10.3892/ijmm.2014.2032
  • Pages: 349-357
  • Copyright: © Zhi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Metastasis is a hallmark of malignant neuroblastoma and is the main reason for therapeutic failure and recurrence of the tumor. The CXC chemokine receptor‑4 (CXCR4), a Gi protein‑coupled receptor for the ligand CXCL12/stromal cell‑derived factor‑1α (SDF‑1α), is expressed in various types of tumor. This receptor mediates the homing of tumor cells to specific organs that express the ligand, CXCL12, for this receptor and plays an important role in tumor growth, invasion, metastasis and angiogenesis. In the present study, the inflammatory cytokine, tumor necrosis factor‑α (TNF‑α) upregulated CXCR4 expression in neuroblastoma cells and increased migration to the CXCR4 ligand SDF‑1α. In addition, this effect was dependent upon NF‑κB transcriptional activity, as blocking the NF‑κB pathway with pyrrolidinedithiocarbamic acid ammonium salt suppressed TNF‑α‑induced upregulation of CXCR4 expression and reduced the migration towards the CXCR4 ligand, SDF‑1α. Treating neuroblastoma cells with TNF‑α resulted in the activation of nuclear factor‑kappa B (NF‑κB) and subsequently, the translocation of NF‑κB from the cytoplasm to the nucleus. Using immunohistochemistry, NF‑κB and CXCR4 were significantly correlated with each other (P=0.0052, Fisher's exact test) in a cohort of neuroblastoma samples (n=80). The present study indicates that the inflammatory cytokine, TNF‑α, partially functions through the NF‑κB signaling pathway to upregulate CXCR4 expression to foster neuroblastoma cell metastasis. These findings indicate that effective inhibition of neuroblastoma metastasis should be directed against the inflammatory cytokine‑induced NF‑κB/CXCR4/SDF‑1α signaling pathway.
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February-2015
Volume 35 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhi Y, Lu H, Duan Y, Sun W, Guan G, Dong Q and Yang C: Involvement of the nuclear factor-κB signaling pathway in the regulation of CXC chemokine receptor-4 expression in neuroblastoma cells induced by tumor necrosis factor-α. Int J Mol Med 35: 349-357, 2015.
APA
Zhi, Y., Lu, H., Duan, Y., Sun, W., Guan, G., Dong, Q., & Yang, C. (2015). Involvement of the nuclear factor-κB signaling pathway in the regulation of CXC chemokine receptor-4 expression in neuroblastoma cells induced by tumor necrosis factor-α. International Journal of Molecular Medicine, 35, 349-357. https://doi.org/10.3892/ijmm.2014.2032
MLA
Zhi, Y., Lu, H., Duan, Y., Sun, W., Guan, G., Dong, Q., Yang, C."Involvement of the nuclear factor-κB signaling pathway in the regulation of CXC chemokine receptor-4 expression in neuroblastoma cells induced by tumor necrosis factor-α". International Journal of Molecular Medicine 35.2 (2015): 349-357.
Chicago
Zhi, Y., Lu, H., Duan, Y., Sun, W., Guan, G., Dong, Q., Yang, C."Involvement of the nuclear factor-κB signaling pathway in the regulation of CXC chemokine receptor-4 expression in neuroblastoma cells induced by tumor necrosis factor-α". International Journal of Molecular Medicine 35, no. 2 (2015): 349-357. https://doi.org/10.3892/ijmm.2014.2032