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Up-Regulation of E-Cadherin by an Anti-Epidermal Growth Factor Receptor Monoclonal Antibody in Lung Cancer Cell Lines¹

National Research Council Canada, Biotechnology Research Institute, Montréal, Québec, H4P 2R2 Canada and Department of Biochemistry, McGill University, Montréal, Québec, Canada [A-E. A., C. Y., M. O-M.]; and Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital, Departments of Medicine and Oncology, and McGill Center for Translational Research in Cancer, Montréal, Québec, H3T 1E2 Canada [M. A. A-J.]

Many human epithelial carcinomas are characterized by the overexpression and constitutive activation of the epidermal growth factor receptor (EGF-R) via an autocrine signaling loop. We have investigated the effects of a ligand-blocking monoclonal antibody (mAb) against the EGF-R LA1 on selected parameters of human lung cancer cell lines (H322 and H661) and normal human bronchial epithelial (NHBE) cells. Using Western blot analysis, we show that H322 and NHBE cell lines express comparable levels of EGF-R/p170erbB-1. The LA1 mAb against EGF-R inhibits growth, induces differentiation to a more epithelial phenotype, reduces the constitutive activation of EGF-R, and up-regulates epithelial cadherin glycoprotein expression in H322 and NHBE cells. In contrast, LA1 had no effect on either growth, differentiation, receptor tyrosine phosphorylation, or the expression of adhesion molecules in H661 cells, which is consistent with our finding that this cell line does not express detectable levels of EGF-R. These studies demonstrate that a blocking anti-EGF-R mAb can regulate proliferation, differentiation, and the expression of cell adhesion molecules in human bronchial epithelial cells. Our findings suggest possible therapeutic avenues for the treatment of invasive carcinomas via the blockade of EGF-R with antibodies.

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