Cyclooxygenase regulates human oropharyngeal carcinomas via the proinflammatory cytokine IL-6: A general role for inflammation?

S. H. Hong, F. G. Ondrey, I. M. Avis, Z. Chen, E. Loukinova, Jr Cavanaugh, C. Van Waes, J. L. Mulshine

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

High levels of prostaglandins are produced in human oropharyngeal carcinoma (OPC). Five human OPC cell lines tested expressed both isoforms of cyclooxygenases (COX). The pan-COX inhibitor ketorolac continuously and significantly decreased PGE2 production and IL-6 and IL-8 levels in all OPC cell lines tested, but did not affect IL-1α, GM-CSF levels, or in vitro tumor cell growth. In contrast, ketorolac reduced OPC growth in vivo. The OPC cell lines used express the IL-6 receptor, and IL-6 stimulation of these cells causes transduction to occur via STAT3 pathway activation. Coincubation with OPC cell lines with conditioned medium from a TPA-exposed HL-60 cells stimulated growth proportional to the IL-6 levels measured in the conditioned medium. This growth effect was specifically inhibited by anti-IL-6 antibody. These results are consistent with cytokine products of inflammatory cells having paracrine growth effects on OPC. If chronic inflammation plays a role in promoting the development of OPC, this mechanism may also apply to other epithelial tumor systems modulated by COX activity.

Original languageEnglish (US)
Pages (from-to)1499-1507
Number of pages9
JournalFASEB Journal
Volume14
Issue number11
DOIs
StatePublished - 2000

Keywords

  • Arachidonic acid
  • COX inhibitors
  • Colon cancer
  • Inflammatory disease

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