Increase of the epidermal growth factor receptor expression by interferon-beta

The epidermal growth factor receptor (EGF-R) is expressed on both normal and malignant epithelial tissue. Recent efforts in cancer therapy use the EGF-R as a target for an antibody therapy. A further increase of the EGF-R expression possibly by interferon (IFN) could improve the efficacy of such an antibody therapy. The effects of IFN on the EGF-R and on the cell proliferation were first evaluated on a human squamous cell carcinoma cell line HLac 79. Several types of IFN were screened for their influence on the receptor expression by flow cytometric studies. IFN-beta caused a doubling of the measured EGF-R expression at a concentration of 100 IU/ml for 48 h. Scatchard analysis with I-125-EGF after IFN treatment showed a doubling of the EGF-R expression and a third of the receptor affinity compared to untreated cells. These alterations were associated with a decrease of the cell proliferation as measured by a bromodeoxyuridine (BrdU) assay. Results were confirmed with xenografts on NMRI nu/nu mice. IFN-beta (intra tumoral) treated xenografts showed a significantly higher amount of EGF-R (393+/-59 fmol/mg protein) and significantly reduced tumour growth compared to untreated xenografts (262+/-51 fmol/mg protein). This study shows that IFN-beta results in an increase of the EGF-R expression in a carcinoma cell line and in xeno-grafts. Cell proliferation is decreased, resulting in reduced growth of the xenograft.