Activity of interferon alpha, interleukin 6 and insulin in the regulation of differentiation in A549 alveolar carcinoma cells.
The differentiation of A549, a human tumour cell line from type II pneumocytes, can be induced by a crude fibroblast-derived factor (FDF) isolated from the conditioned medium of glucocorticoid-treated lung fibroblasts. In the present report, we have used alkaline phosphatase as a differentiation marker to investigate the activity of a number of growth factors as potential candidates for this paracrine activity. This showed that insulin, interleukin 6 (IL-6), and interferon alpha (IFN-alpha) could simulate the activity of conditioned medium. Their effects were dexamethasone (DX) dependent, additive and reversible with a half-life of 1 week. Transforming growth factor alpha and beta, IL-1 alpha and epidermal growth factor, were all inhibitory, and inhibition was opposed, partially or completely, by DX. The most potent inducer was IL-6, but as DX was shown to decrease the concentration of IL-6 in lung fibroblast-conditioned medium it seems an unlikely candidate for FDF. Unlike FDF, all of the positive-acting factors were shown to induce plasminogen activator. FDF has also been shown to be active in the absence of DX. This suggests that differentiation-inducing activity may be present in several paracrine factors, but that so far a candidate for FDF has not been identified.
CRC Department of Medical Oncology, University of Glasgow, Bearsden, UK.
C
C
McCormick
R I
RI
Freshney
V
V
Speirs
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000473:pathology*; D000469:Alkaline Phosphatase / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008168:Lung / Q000166:cytology; D008175:Lung Neoplasms / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis; D010960:Plasminogen Activators / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects
D014408:Biomarkers, Tumor; D017077:Culture Media, Conditioned; D016207:Cytokines; D006133:Growth Substances; D007328:Insulin; D016898:Interferon-alpha; D015850:Interleukin-6; D009363:Neoplasm Proteins; D003907:Dexamethasone; D000469:Alkaline Phosphatase; D010960:Plasminogen Activators