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Article

Hypoxia regulates Toll‑like receptor‑9 expression and invasive function in human brain cancer cells in vitro

  • Authors:
    • Jouko Sandholm
    • Johanna Tuomela
    • Joonas H. Kauppila
    • Kevin W. Harris
    • David Graves
    • Katri S. Selander
  • View Affiliations / Copyright

    Affiliations: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA, Department of Pathology, Oulu University Hospital, Oulu 90029, Finland, Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA
  • Pages: 266-274
    |
    Published online on: April 25, 2014
       https://doi.org/10.3892/ol.2014.2095
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Abstract

Toll‑like receptor‑9 (TLR9) is a cellular DNA sensor of the innate immune system. TLR9 is widely expressed in a number of tumors, including brain cancer; however, little is known regarding its regulation and involvement in cancer pathophysiology. The present study demonstrated that hypoxia upregulates and downregulates TLR9 expression in human brain cancer cells in vitro, in a cell‑specific manner. In addition, hypoxia‑induced TLR9 upregulation was associated with hypoxia‑induced invasion; however, such invasion was not detected in cells where hypoxia had suppressed TLR9 expression. Furthermore, suppression of TLR9 expression through TLR9 siRNA resulted in an upregulation of matrix metalloproteinase (MMP)‑2, ‑9 and ‑13 and tissue inhibitor of matrix metalloproteinases‑3 (TIMP‑3) mRNA, and a decreased invasion of cells in normoxia, in a cell‑specific manner. In cells where hypoxia induced TLR9 expression, TLR9 expression and invasion were reduced by TLR9 siRNA. The decreased invasion observed in hypoxia was associated with the decreased expression of the MMPs and a concomitant increase in TIMP‑3 expression. In conclusion, hypoxia regulates the invasion of brain cancer cells in vitro in a TLR9‑dependent manner, which is considered to be associated with a complex expression pattern of TLR9‑regulated mediators and inhibitors of invasion.
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Copy and paste a formatted citation
Spandidos Publications style
Sandholm J, Tuomela J, Kauppila JH, Harris KW, Graves D and Selander KS: Hypoxia regulates Toll‑like receptor‑9 expression and invasive function in human brain cancer cells in vitro. Oncol Lett 8: 266-274, 2014.
APA
Sandholm, J., Tuomela, J., Kauppila, J.H., Harris, K.W., Graves, D., & Selander, K.S. (2014). Hypoxia regulates Toll‑like receptor‑9 expression and invasive function in human brain cancer cells in vitro. Oncology Letters, 8, 266-274. https://doi.org/10.3892/ol.2014.2095
MLA
Sandholm, J., Tuomela, J., Kauppila, J. H., Harris, K. W., Graves, D., Selander, K. S."Hypoxia regulates Toll‑like receptor‑9 expression and invasive function in human brain cancer cells in vitro". Oncology Letters 8.1 (2014): 266-274.
Chicago
Sandholm, J., Tuomela, J., Kauppila, J. H., Harris, K. W., Graves, D., Selander, K. S."Hypoxia regulates Toll‑like receptor‑9 expression and invasive function in human brain cancer cells in vitro". Oncology Letters 8, no. 1 (2014): 266-274. https://doi.org/10.3892/ol.2014.2095
Copy and paste a formatted citation
x
Spandidos Publications style
Sandholm J, Tuomela J, Kauppila JH, Harris KW, Graves D and Selander KS: Hypoxia regulates Toll‑like receptor‑9 expression and invasive function in human brain cancer cells in vitro. Oncol Lett 8: 266-274, 2014.
APA
Sandholm, J., Tuomela, J., Kauppila, J.H., Harris, K.W., Graves, D., & Selander, K.S. (2014). Hypoxia regulates Toll‑like receptor‑9 expression and invasive function in human brain cancer cells in vitro. Oncology Letters, 8, 266-274. https://doi.org/10.3892/ol.2014.2095
MLA
Sandholm, J., Tuomela, J., Kauppila, J. H., Harris, K. W., Graves, D., Selander, K. S."Hypoxia regulates Toll‑like receptor‑9 expression and invasive function in human brain cancer cells in vitro". Oncology Letters 8.1 (2014): 266-274.
Chicago
Sandholm, J., Tuomela, J., Kauppila, J. H., Harris, K. W., Graves, D., Selander, K. S."Hypoxia regulates Toll‑like receptor‑9 expression and invasive function in human brain cancer cells in vitro". Oncology Letters 8, no. 1 (2014): 266-274. https://doi.org/10.3892/ol.2014.2095
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