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Lymphoma

COX-2-dependent PGE2 acts as a growth factor in mycosis fungoides (MF)

Abstract

Cancer often originates from a site of persistent inflammation, and the mechanisms turning chronic inflammation into a driving force of carcinogenesis are intensely investigated. Cyclooxygenase-2 (COX-2) is an inducible key modulator of inflammation that carries out the rate-limiting step in prostaglandin synthesis. Aberrant COX-2 expression and prostaglandin E2 (PGE2) production have been implicated in tumorigenesis. In this study we show that COX-2 is ectopically expressed in malignant T-cell lines from patients with cutaneous T-cell lymphoma (CTCL) as well as in situ in lymphocytic cells in 21 out of 22 patients suffering from mycosis fungoides (MF) in plaque or tumor stage. COX-2 is not expressed in lymphocytes of 11 patients with patch-stage MF, whereas sporadic COX-2 staining of stromal cells is observed in the majority of patients. COX-2 expression correlates with a constitutive production of PGE2 in malignant T cells in vitro. These cells express prostaglandin receptors EP3 and EP4 and the receptor antagonist as well as small interfering RNA (siRNA) directed against COX-2, and specific COX-2 inhibitors strongly reduce their spontaneous proliferation. In conclusion, our data indicate that COX-2 mediated PGE2 exerts an effect as a tumor growth factor in MF.

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Acknowledgements

This work was supported in part by the Danish Research Councils, the Danish Cancer Society (Kræftens Bekæmpelse), the Lundbeck Foundation, the Novo Nordic Foundation, the AP Møller Foundation for the Advancement of Medical Science (Fonden til Lægevidenskabenskabene Fremme), the Neye Foundation (Neye Fonden), the Danish Foundation for Advanced Technology (Højteknologifonden) and the Beckett Foundation (Beckett Fonden).

Author contributions:

KLMK, AW, JCB and NØ designed the research; KLMK, AW and CSK performed the research; KLMK, AW, CSK, BL, TK, KWE, QZ, MAW, CG, ER, JCB and NØ analyzed data; and KLMK, JCB, MAW, NØ and AW wrote the paper.

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Correspondence to A Woetmann.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on the Leukemia website

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Kopp, K., Kauczok, C., Lauenborg, B. et al. COX-2-dependent PGE2 acts as a growth factor in mycosis fungoides (MF). Leukemia 24, 1179–1185 (2010). https://doi.org/10.1038/leu.2010.66

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  • DOI: https://doi.org/10.1038/leu.2010.66

Keywords

  • COX-2
  • prostaglandin
  • CTCL
  • diagnosis
  • proliferation

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