Abnormal interleukin 10Ralpha expression contributes to the maintenance of elevated cyclooxygenase-2 in non-small cell lung cancer cells.
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.
Heuze-Vourc'h
Nathalie
N
University of California at Los Angeles Lung Cancer Research Program, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California 90095, USA.
Zhu
Li
L
Krysan
Kostyantyn
K
Batra
Raj K
RK
Sharma
Sherven
S
Dubinett
Steven M
SM
D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D051546:Cyclooxygenase 2; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008565:Membrane Proteins; D017472:Receptors, Interleukin-1; D016753:Interleukin-10; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases