GROWTH INHIBITORY EFFECTS OF INTERFERON-BETA BUT NOT INTERFERON-ALPHA ON HUMAN GLIOMA-CELLS - CORRELATION OF RECEPTOR-BINDING, 2',5'-OLIGOADENYLATE SYNTHETASE AND PROTEIN-KINASE ACTIVITY

The antiproliferative effects of human recombinant interferon-α (r IFN-α A) and interferon-β (rIFN-βser) were assessed in vitro against seven human glioma cell lines. Further analysis of one of these lines (EFC-2) in response to rIFN-αA demonstrated a minimum growth inhibition by day 6 of treatment, whereas a 50% inhibition of cell growth was observed with a dose of 50 U/ml of IFN-βser. No significant growth inhibition was seen by rIFN-αA at doses up to 500 U/ml. Addition of rIFN-αA to rIFN-βser-treated EFC-2 cells neither suppressed nor augmented the antiproliferative response to IFN-βser. The binding of 125I-labeled rIFN-αA or 125I-labeled rIFN-βser to EFC-2 cells was inhibited competitively by increasing concentrations of either unlabeled rIFN-αA or rIFN-βser. This suggests that the cellular receptors for both rIFN-αA and rIFN-βser appear to be intact and appear to bind both agents equally. Furthermore, incubation of EFC-2 cells for 72 h with either rIFN-αA or rIFN-βser resulted in an increase in 2′,5′-oligoadenylate (2-5A) synthetase activity 5-fold with rIFN-αA and 50-fold with rIFN-βser. Similarly, the 68-kD IFN-induced protein kinase was induced substantially with rIFN-βser but only slightly induced with rIFN-αA treatment. These results suggest that EFC-2 human glioma cells demonstrate a differential sensitivity in terms of growth inhibition to rIFN-βser and to rIFN-αA which appears to correlate with a differential induction of both intracellular 2-5A synthetase and protein kinase activity. These results cannot be explained solely on the basis of surface receptor binding of rIFN-αA and rIFN-βser. These data do suggest that, for human glioma cells in culture, type I IFN receptors may display a subtle architectural variation that allows equivalent binding of both IFN-α and IFN-βser, but allows an enhanced signal transduction and biological effect only after binding a specific IFN subtype. © 1990, Mary Ann Liebert, Inc. All rights reserved.