Abstract
Non-small cell lung cancer (NSCLC) cells are known to constitutively overexpress cyclooxygenase (COX)-2. Tumor COX-2-dependent production of PGE(2) 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 PGE(2) production in NSCLC cells. Although normal human bronchial epithelial cells expressed both intracellular and membrane IL-10Ralpha, NSCLC cells only expressed intracellular but not cell surface membrane IL-10Ralpha. Unresponsiveness of COX-2 to IL-10 is due to the deficiency of IL-10Ralpha on the surface of NSCLC cells. Our findings highlight a novel mechanism contributing to maintenance of elevated COX-2 and PGE(2) in the lung tumor environment.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Carcinoma, Non-Small-Cell Lung / enzymology*
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Carcinoma, Non-Small-Cell Lung / genetics
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Carcinoma, Non-Small-Cell Lung / metabolism
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Cell Membrane / metabolism
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Cyclooxygenase 2
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Down-Regulation
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Gene Expression Regulation, Enzymologic
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Gene Expression Regulation, Neoplastic
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Humans
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Interleukin-10 / physiology
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Isoenzymes / biosynthesis*
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Isoenzymes / genetics
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Lung Neoplasms / enzymology*
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Lung Neoplasms / genetics
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Lung Neoplasms / metabolism
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Membrane Proteins
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Prostaglandin-Endoperoxide Synthases / biosynthesis*
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Prostaglandin-Endoperoxide Synthases / genetics
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Receptors, Interleukin-1 / biosynthesis*
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Receptors, Interleukin-1 / physiology
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Cells, Cultured
Substances
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Isoenzymes
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Membrane Proteins
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Receptors, Interleukin-1
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Interleukin-10
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases