PREVENTION OF EGF-MODULATED ADHESION OF TUMOR-CELLS TO MATRIX PROTEINS BY SPECIFIC EGF RECEPTOR INHIBITION

The adhesion of tumor cells to various extracellular matrix (ECM) prot eins is influenced by epidermal growth factor (EGF). Maximal effects a re obtained at low EGF concentrations, at which mostly the cytoskeleto n-associated high-affinity EGF receptors (EGFRs) are saturated. Tumor cells expressing EGFR either endogenously (MDA MB 231, MTLn3) or, for the human EGFR, ectopically (MTC HER1/1) in intermediate amounts exhib ited, upon EGF addition, increased cellular adhesion to various ECM pr oteins, such as fibronectin, collagens and vitronectin. In contrast, h uman A431 and MDA MB 468 cells, over expressing EGFR, demonstrated red uced attachment in similar experimental conditions, Both increased as well as reduced EGF-dependent adhesion could be blocked using either l igand-blocking monoclonal antibody 14E1 or the potent EGFR tyrosine ki nase inhibitor PD 153035. Our data indicate that signals downstream of EGFR activation are responsible for the opposing effects of EGF on ce llular adhesion since both can be prevented by EGFR inhibition, Thus, the integration of EGFR- and integrin-dependent signals can be differe nt in carcinoma cell lines and might be influenced by EGFR numbers. (C ) 1998 Wiley-Liss, Inc.