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 impede proliferation and induce differentiation of head and neck squamous cell carcinoma. To test this hypothesis, we examined the effect of monoclonal antibody 528 directed against epidermal growth factor receptor on the proliferation and differentiation of monolayer cells and multicenter tumor spheroids from three head and neck squamous cell carcinoma cell lines (1483, MDA 686Ln, and MDA 886Ln) and the epidermal growth factor-responsive vulvar carcinoma A431. All head and neck squamous cell carcinoma lines were shown to express high levels of epidermal growth factor receptor by Scatchard analyses. Epidermal growth factor inhibited the growth of monolayer cells but stimulated the growth of 886 and A431 multicellular tumor spheroids. Epidermal growth factor modulated the differentiation of A431 and 686 with respect to involucrin immunohistochemistry and cornified enveloped competency. Monoclonal antibody 528 directed against epidermal growth factor receptor inhibited cellular proliferation as measured by cell number, thymidine incorporation, and multicellular tumor spheroid volume. A mild promotion of differentiation was observed in the epidermal growth factor-responsive cells. In conclusion, monoclonal antibody 528 directed against epidermal growth factor receptor inhibits growth of head and neck squamous cell carcinoma cells bearing high levels of epidermal growth factor receptors and promotes differentiation in some tumors. The use of a multicellular tumor spheroid model to evaluate growth factor responsiveness and inhibition of proliferation may more accurately reflect in vivo tumor growth than monolayer cells. Antibodies against epidermal growth factor receptor may prove effective in modulating disease progression in patients with head and neck squamous cell carcinoma.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York.
E M
EM
Sturgis
P G
PG
Sacks
H
H
Masui
J
J
Mendelsohn
S P
SP
Schantz
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D004815:Epidermal Growth Factor; D066246:ErbB Receptors