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COX2 expression in neuroblastoma increases tumorigenicity but does not affect cell death in response to the COX2 inhibitor celecoxib

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Abstract

COX2 is an inducible cyclooxygenase implicated in the metastasis and migration of tumour cells. In neuroblastoma, COX2 expression has been detected in both cell lines and tumours. The treatment of neuroblastoma cells in vitro with celecoxib, a COX2 inhibitor, induces apoptosis. The aim of this study was to investigate the role of COX2 in neuroblastoma tumour biology by creating a cell line in which COX2 could be conditionally expressed. Xenograft studies showed that the conditional expression of COX2 enhanced tumour growth and malignancy. Elevated COX2 expression enhanced the proliferation and migration of neuroblastoma cells in vitro. However, elevated COX2 expression or variation between cell lines did not affect sensitivity to the COX2 inhibitor celecoxib, indicating that celecoxib does not promote cell death through COX2 inhibition. These data show that increased COX2 expression alone can enhance the tumorigenic properties of neuroblastoma cells; however, high levels of COX2 may not be a valid biomarker of sensitivity to non-steroidal anti-inflammatory drugs such as celecoxib.

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Abbreviations

AA:

Arachidonic acid

COX:

Cyclooxygenase

Dox:

Doxycycline

NSAIDs:

Non-steroidal anti-inflammatory drugs

PGE2:

Prostaglandin E2

Tet:

Tetracycline

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Acknowledgements

Dr. E. Bell was funded by SPARKs (Grant Number: 08NCL01), Dr. F. Ponthan was supported by the Swedish Children’s Cancer Foundation and the Neuroblastoma Society, UK. We would also like to thank Pfizer for providing the celecoxib and Simon Bomken and Olaf Heidenreich for the lentiviral vector.

Conflict of interest

There are no conflicts of interest concerning this manuscript.

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Authors and Affiliations

  1. Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK

    Emma Bell, Frida Ponthan, Claire Whitworth, Deborah A. Tweddle, John Lunec & Christopher P. F. Redfern

  2. Division of Neuroblastoma Genomics (B087), German Cancer Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Emma Bell

Authors
  1. Emma Bell
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  2. Frida Ponthan
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  3. Claire Whitworth
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  4. Deborah A. Tweddle
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  5. John Lunec
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  6. Christopher P. F. Redfern
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Correspondence to Christopher P. F. Redfern.

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Bell, E., Ponthan, F., Whitworth, C. et al. COX2 expression in neuroblastoma increases tumorigenicity but does not affect cell death in response to the COX2 inhibitor celecoxib. Clin Exp Metastasis 31, 651–659 (2014). https://doi.org/10.1007/s10585-014-9656-3

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  • DOI: https://doi.org/10.1007/s10585-014-9656-3

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