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

High levels of prostaglandins are produced in human oropharyngeal carcinoma (OPC), Five human OPC cell lines tested expressed both isoforms of cycloox ygenases (COX), The pan-COX inhibitor ketorolac continuously and significan tly decreased PGE(2) production and IL-6 and IL-8 levels in all OPC cell li nes tested, but did not affect IL-1 alpha, GM-CSF levels, or in vitro tumor cell growth. In contrast, ketorolac reduced OPC growth in vivo. The OPC ce ll lines used express the IL-6 receptor, and IL-6 stimulation of these cell s causes transduction to occur via STAT3 pathway activation. Coincubation w ith OPC cell lines with conditioned medium from a TPA-exposed HL-60 cells s timulated growth proportional to the IL-6 levels measured in the conditione d medium. This growth effect was specifically inhibited by anti-IL-6 antibo dy. These results are consistent with cytokine products of inflammatory cel ls 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.