Autonomous Expressions of Cytokine Genes by Human Lung Cancer Cells and Their Paracrine Regulation

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Abstract
Cell‐to‐cell interaction between tumors and host inflammatory cells is important for the subsequent cancer progression or regression. We examined the expressions of mRNAs for various proinflammatory cytokines by nine human lung cancer cell lines and the influences of cytokines on their gene expressions. The cytokines used were interleukin 1β (IL‐1β), interleukin 6 (IL‐6), tumor necrosis factor α (TNF‐α), granulocyte‐macrophage colony stimulating factor (GM‐CSF) and monocyte chemotactic and activating factor. Gene expressions of cytokines were measured by Northern blot analysis. Substantial expressions of cytokine genes were detected in several lung cancer cell lines such as RERF‐LC‐MS, RERF‐LC‐OK and VMRC‐LCD, although the levels of expression of each cytokine varied in different cell lines. Four lung cancer cell lines (RERF‐LC‐MS, RERF‐LC‐OK, A549 and YO‐88) were used to examine the effects of exogenous cytokines (IL‐1β, TNF‐α and GM‐CSF) on cytokine gene expressions by the cells. TNF‐α and IL‐1β caused significant changes in the levels of mRNA expressions of certain cytokines. Moreover, on stimulation with TNF‐α, RERF‐LC‐OK cells produced IL‐6 extracellularly. These extensive differences in the levels of gene expressions and productions of cytokines could have profound effects on the interactions between human lung cancer cells and the corresponding host cells.