Targeting ErbB-1 and ErbB-4 in irradiated head and neck cancer: results of in vitro and in vivo studies.

Abstract

ErbB oncogenes have a major role in cancer. The role of ErbB-4 in cancer cell biology and the effect of anti-ErbB-1 and anti-ErbB-4 monoclonal antibodies were evaluated in this study. ErbB-4 expression and binding was evaluated by Western blot, enzyme-linked immunosorbent assay (ELISA), fluorescent microscopy, and flow cytometry. Cell survival was measured by XTT assay. Tumor progression was followed up in nude mice model. High ErbB-1 levels in head and neck cancer cell lines were determined, whereas ErbB-4 expression varied. Specific antibody binding to the cells was demonstrated. High ErbB-4 expressing squamous cell carcinoma 1 (SCC-1) cells proliferated faster and generated faster growing tumors in mice. Cetuximab and mAb-3 reduced cell survival proportional to ErbB-1 and ErbB-4 expression. Combination of antibodies with irradiation was most effective in reducing cell survival and tumor growth. ErbB-4 plays a role in head and neck cancer cell biology. Anti-ErbB-4 targeted therapy can serve as a new strategy against head and neck cancer when combined with established treatments.