Monoclonal antibody 425 inhibits growth stimulation of carcinoma cells by exogenous EGF and tumor‐derived EGF/TGF‐α

Publisher Website
Google Scholar
Abstract
Carcinoma cells frequently coexpress transforming growth factor (TGF)‐α and its receptor, the epidermal growth factor (EGF) receptor, implicating an autocrine function of carinoma‐derived TGF‐α. Using a monoclonal antibody (425) to the EGF‐receptor, we investigated the role of exogenous and tumor cell‐derived EGF/TGF‐α mitogenic activities in proliferation of cell lines derived from solid tumors. Monoclonal antibody 425 was chosen for these studies because it inhibits binding of EGF/TGF‐α to the EGF‐receptor and effectively blocks activation of the EGF‐receptor by EGF/TGF‐α. Seven malignant cell lines originating from carcinomas of colon, pancreas, breast, squamous epithelia, and bladder expressed surface EGF‐receptor and secreted EGF/TGF‐α‐like mitogenic activities into their tissue culture media. All cell lines were maintained in a defined medium free of exogenous EGF/TGF‐α. EGF and TGF‐α added to the culture medium stimulated proliferation of five cell lines to comparable levels. EGF/TGF‐α‐dependent proliferation was significantly reduced by addition of MAb 425 to culture media. In addition, monoclonal antibody 425 reduced proliferation of the five EGF/TGF‐α responsive cell lines in the absence of exogenous EGF/TGF‐α. Antiproliferative effects induced by monoclonal antibody 425 were reversible and could be overcome by addition of EGF to culture media. Our results indicate that tumor‐derived EGF‐receptor‐reactive mitogens can promote proliferation of carcinoma cells in an autocrine fashion.

This publication has 24 references indexed in Scilit: