EFFECTS OF ANTIEPIDERMAL GROWTH-FACTOR RECEPTOR ANTIBODY-528 ON THE PROLIFERATION AND DIFFERENTIATION OF HEAD-AND-NECK-CANCER

Antibodies directed against the epidermal growth factor receptor may i mpede proliferation and induce differentiation of head and neck squamo us cell carcinoma. To test this hypothesis, we examined the effect of monoclonal antibody 528 directed against epidermal growth factor recep tor on the proliferation and differentiation of monolayer cells and mu lticellular tumor spheroids from three head and neck squamous cell car cinoma cell lines (1483, MDA 686Ln, and MDA 886Ln) and the epidermal g rowth factor-responsive vulvar carcinoma A431. All head and neck squam ous cell carcinoma lines were shown to express high levels of epiderma l growth factor receptor by Scatchard analyses. Epidermal growth facto r inhibited the growth of monolayer cells but stimulated the growth of 886 and A431 multicellular tumor spheroids. Epidermal growth factor m odulated the differentiation of A431 and 686 with respect to involucri n immunohistochemistry and cornified envelope competency. Monoclonal a ntibody 528 directed against epidermal growth factor receptor inhibite d cellular proliferation as measured by cell number, thymidine incorpo ration, and multicellular tumor spheroid volume. A mild promotion of d ifferentiation was observed in the epidermal growth factor-responsive cells. In conclusion, monoclonal antibody 528 directed against epiderm al growth factor receptor inhibits growth of head and neck squamous ce ll carcinoma cells bearing high levels of epidermal growth factor rece ptors and promotes differentiation in some tumors. The use of a multic ellular tumor spheroid model to evaluate growth factor responsiveness and inhibition of proliferation may more accurately reflect in vivo tu mor growth than monolayer cells. Antibodies against epidermal growth f actor receptor may prove effective in modulating disease progression i n patients with head and neck squamous cell carcinoma.