Human renal cancers resistant to IFN's antiproliferative action exhibit sensitivity to IFN's gene-inducing and antiviral actions.

Overview

PURPOSE: Although treatment with interferon-alpha (IFN alpha) results in tumor regression in a subset (< 20%) of patients with renal cell carcinoma, the underlying mechanisms for the resistance of renal cancer (RC) cells to IFN alpha is unknown. MATERIALS AND METHODS: We examined 5 RC lines resistant and 5 RC lines sensitive to the antiproliferative effects of IFN alpha for differences in: 1) the number of IFN binding sites, 2) the number of signal-transducing IFNAR-1 chains of the IFN alpha receptor, 3) IFN alpha receptor structure, 4) IFN-stimulated gene (ISG) expression and 5) IFN alpha sensitivity in antiviral assays. RESULTS: No structural alterations in the IFN alpha receptor were detected in any RC line examined, although varying numbers of ligand binding sites and IFNAR-1 signal transducer chains were present. All 5 IFN-sensitive, and 4 of 5 IFN-resistant RC lines were sensitive to the antiviral and gene-inducing actions of IFN alpha. CONCLUSIONS: The resistance of RC lines to IFN's antiproliferative action is not due to defects in ligand binding or in IFN-receptor structure. Our results indicate that the defective antiproliferative response in most RC cells is not due to their failure to induce the gene-inducing and antiviral effects of IFN alpha.