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Prevention of EGF‐modulated adhesion of tumor cells to matrix proteins by specific EGF receptor inhibition
Author(s) -
Genersch Elke,
Schneider Douglas W.,
Sauer Gerhard,
Khazaie Kashayarsha,
Schuppan Detlef,
Lichtner Rosemarie B.
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980119)75:2<205::aid-ijc7>3.0.co;2-y
Subject(s) - fibronectin , vitronectin , epidermal growth factor , extracellular matrix , integrin , microbiology and biotechnology , a431 cells , epidermal growth factor receptor , cell adhesion , adhesion , biology , focal adhesion , receptor , chemistry , cancer research , signal transduction , cell , biochemistry , oncogene , cell cycle , organic chemistry
The adhesion of tumor cells to various extracellular matrix (ECM) proteins is influenced by epidermal growth factor (EGF). Maximal effects are obtained at low EGF concentrations, at which mostly the cytoskeleton‐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 exhibited, upon EGF addition, increased cellular adhesion to various ECM proteins, such as fibronectin, collagens and vitronectin. In contrast, human A431 and MDA MB 468 cells, over‐expressing EGFR, demonstrated reduced attachment in similar experimental conditions. Both increased as well as reduced EGF‐dependent adhesion could be blocked using either ligand‐blocking monoclonal antibody 14E1 or the potent EGFR tyrosine kinase inhibitor PD 153035. Our data indicate that signals downstream of EGFR activation are responsible for the opposing effects of EGF on cellular adhesion since both can be prevented by EGFR inhibition. Thus, the integration of EGFR‐ and integrin‐dependent signals can be different in carcinoma cell lines and might be influenced by EGFR numbers. Int. J. Cancer 75:205–209, 1998. © 1998 Wiley‐Liss, Inc.