Aberrant NF-κB activity is critical in focal necrosis formation of human glioblastoma by regulation of the expression of tissue factor

  • Authors:
    • Tong-Xin Xie
    • Kenneth D. Aldape
    • Weida Gong
    • Takao Kanzawa
    • Dima Suki
    • Seiji Kondo
    • Frederick Lang
    • Francis Ali-Osman
    • Raymond Sawaya
    • Suyun Huang
  • View Affiliations

  • Published online on: July 1, 2008     https://doi.org/10.3892/ijo.33.1.5
  • Pages: 5-15
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Abstract

Focal necrosis is a key pathologic feature that distinguishes glioblastoma from lower grade glioma. The presence of necrosis in a glioblastoma could promote its rapid growth and clinical progression. Focal necrosis of glioblastoma seems to be associated with thrombosis that result from hyper-coagulability. In the present study, we found that glioblastoma cells had a high level of constitutive nuclear factor (NF)-κB activity, which was directly correlated with necrosis in glioblastomas. We also found a direct correlation between NF-κB activity and the expression of tissue factor (TF), a potent procoagulant factor in gliomas. Inhibition of TF by an inhibitory antibody prevented the procoagulant activity of glioblastoma cells, indicating a TF-dependent mechanism. Blockade of NF-κB activation significantly inhibited TF expression and the procoagulant activity of glioblastoma cells in vitro. Blockade of NF-κB activation also significantly inhibited in vivo expression of TF, which was directly correlated with decreased necrosis formation and tumor growth of glioblastoma cells in nude mice. Collectively, these results suggest that elevated NF-κB activity in glioblastomas cells plays a critical role in necrosis formation of glioblastoma and that inhibition of NF-κB activity in glioblastoma can suppress necrosis formation and progressive growth.

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July 2008
Volume 33 Issue 1

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

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Spandidos Publications style
Xie T, Aldape KD, Gong W, Kanzawa T, Suki D, Kondo S, Lang F, Ali-Osman F, Sawaya R, Huang S, Huang S, et al: Aberrant NF-κB activity is critical in focal necrosis formation of human glioblastoma by regulation of the expression of tissue factor. Int J Oncol 33: 5-15, 2008
APA
Xie, T., Aldape, K.D., Gong, W., Kanzawa, T., Suki, D., Kondo, S. ... Huang, S. (2008). Aberrant NF-κB activity is critical in focal necrosis formation of human glioblastoma by regulation of the expression of tissue factor. International Journal of Oncology, 33, 5-15. https://doi.org/10.3892/ijo.33.1.5
MLA
Xie, T., Aldape, K. D., Gong, W., Kanzawa, T., Suki, D., Kondo, S., Lang, F., Ali-Osman, F., Sawaya, R., Huang, S."Aberrant NF-κB activity is critical in focal necrosis formation of human glioblastoma by regulation of the expression of tissue factor". International Journal of Oncology 33.1 (2008): 5-15.
Chicago
Xie, T., Aldape, K. D., Gong, W., Kanzawa, T., Suki, D., Kondo, S., Lang, F., Ali-Osman, F., Sawaya, R., Huang, S."Aberrant NF-κB activity is critical in focal necrosis formation of human glioblastoma by regulation of the expression of tissue factor". International Journal of Oncology 33, no. 1 (2008): 5-15. https://doi.org/10.3892/ijo.33.1.5