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Abnormal Interleukin 10R Expression Contributes to the Maintenance of Elevated Cyclooxygenase-2 in Non-Small Cell Lung Cancer Cells¹

University of California at Los Angeles Lung Cancer Research Program of the Jonsson Comprehensive Cancer Center and the Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at University of California at Los Angeles, and the Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California 90095

Non-small cell lung cancer (NSCLC) cells are known to constitutively overexpress cyclooxygenase (COX)-2. Tumor COX-2-dependent production of PGE₂ triggers the synthesis of lymphocyte and macrophage interleukin (IL)-10 that, in turn, is known to potently suppress COX-2 in normal cells. Thus, we investigated the capacity of IL-10 to down-regulate COX-2 expression in NSCLC cells. Western blotting and ELISA analyses revealed that IL-10 did not affect COX-2 expression and subsequent PGE₂ production in NSCLC cells. Although normal human bronchial epithelial cells expressed both intracellular and membrane IL-10R, NSCLC cells only expressed intracellular but not cell surface membrane IL-10R. Unresponsiveness of COX-2 to IL-10 is due to the deficiency of IL-10R on the surface of NSCLC cells. Our findings highlight a novel mechanism contributing to maintenance of elevated COX-2 and PGE₂ in the lung tumor environment.

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