Activity of growth factors in the IL-6 group in the differentiation of human lung adenocarcinoma

The role of the interleukin-6 (IL-6) group of cytokines in differentiation of two lung adenocarcinoma cell lines has been examined using induction of alkaline phosphatase and expression of surfactant protein A. Oncostatin M w as the most active and potent for alkaline phosphatase in A549 cells, with IL-6 having similar activity but less potency, Neither cytokine induced alk aline phosphatase in NCI-H441 cells, although induction was obtained with l ung fibroblast-conditioned medium. Surfactant protein A was induced in NCI- H441 cells by conditioned medium and dexamethasone and, to a much lesser ex tent, by oncostatin M or IL-6, Induction of alkaline phosphatase and surfac tant protein A were both dexamethasone-dependent, though some induction of surfactant protein A was obtained with interferon-alpha in the absence of d examethasone. The activity present in lung fibroblast-conditioned medium su ggests paracrine control, but this appears not to be due to oncostatin M or IL-6 as disabling antibodies to either cytokine were not inhibitory, and, although alkaline phosphatase was induced in A549 by both cytokines, it was only induced by conditioned medium in NCI-H441 cells. Furthermore, surfact ant protein A was induced in H441 by conditioned medium to a much greater e xtent than by oncostatin M or IL-6. These data demonstrate that cytokines o f the IL-6 group have potential as differentiation inducers in lung adenoca rcinoma cells and that there is an equivalent paracrine factor(s) in lung f ibroblast conditioned medium. As the production of this factor by fibroblas ts is not enhanced by glucocorticoid, although the response of the target c ell is, it would appear to be distinct from the fibrocyte pneumocyte factor previously described by Post et at 1984 Nature 308: 284-286. (C) 2000 Canc er Research Campaign.