Mechanisms of resistance off NSCLC to interferons

Abstract

Interferons (IFNs) are naturally occurring cytokines which have pleiotropic actions including regulation of cell growth and differentiation, important for control of tumour growth and development. In this study we investigated the association between the presence of IFN genes in NSCLC cell lines, receptor expression and function, and sensitivity to IFNs. Some of the NSCLC lines had partial or complete IFN gene deletion but others contained all genes. However, all NSCLC lines were resistant to the antiproliferative effects of IFN alpha 2 and IFN beta ser. While the lack of sensitivity to IFNs did not appear to be associated with the presence of IFN genes, numbers of receptors or with low binding affinities it did correlate with abnormal regulation of receptor expression. When analyzed by Northern blotting it was notable that IFNA receptor expression on a sensitive cell line, Daudi, was upregulated following IFN exposure however, in the insensitive NSCLC lines IFN mediated upregulation of receptors did not occur. This defect in the regulation of receptor expression in NSCLC lines could contribute to the insensitivity of the antiproliferative effects of IFN's and thus potentiate tumour development or progression.