Regular Article

British Journal of Cancer (2000) 82, 881–890. doi:10.1054/bjoc.1999.1015 www.bjcancer.com
Published online 20 January 2000

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

C McCormick1 and R I Freshney1

1CRC Department of Medical Oncology, University of Glasgow, Alexander Stone Building, Garscube Estate, Bearsden, Glasgow, G61 1BD, UK

Received 16 September 1999; Revised 5 October 1999; Accepted 19 October 1999.

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Abstract

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 was the most active and potent for alkaline phosphatase in A549 cells, with IL-6 having similar activity but less potency. Neither cytokine induced alkaline phosphatase in NCI-H441 cells, although induction was obtained with lung fibroblast-conditioned medium. Surfactant protein A was induced in NCI-H441 cells by conditioned medium and dexamethasone and, to a much lesser extent, by oncostatin M or IL-6. Induction of alkaline phosphatase and surfactant protein A were both dexamethasone-dependent, though some induction of surfactant protein A was obtained with interferon-alpha in the absence of dexamethasone. The activity present in lung fibroblast-conditioned medium suggests 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, surfactant protein A was induced in H441 by conditioned medium to a much greater extent than by oncostatin M or IL-6. These data demonstrate that cytokines of the IL-6 group have potential as differentiation inducers in lung adenocarcinoma cells and that there is an equivalent paracrine factor(s) in lung fibroblast conditioned medium. As the production of this factor by fibroblasts is not enhanced by glucocorticoid, although the response of the target cell is, it would appear to be distinct from the fibrocyte pneumocyte factor previously described by Post et al 1984 Nature: 284–286. © 2000 Cancer Research Campaign

Keywords:

differentiation, interleukin-6, oncostatin M, NSCLC, alkaline phosphatase, SPA

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