Production of epidermal growth factor related ligands in tumorigenic and benign human lung epithelial cells

We recently demonstrated that human lung epithelial cells, overexpressing E rbB-2, formed tumors in nude mice only when high levels of transforming gro wth factor alpha (TGF alpha) were produced. Cells transfected with a TGF al pha antisense vector failed to form tumors in nude mice. In order to furthe r evaluate the importance, for tumorigenicity, of TGF alpha and its stimula tion of ErbB family signalling, the production of other EGF family growth f actors by these human lung epithelial cells was studied. We demonstrate for the first time that both tumorigenic and non-tumorigenic human lung epithe lial cells produced, in addition to TGF alpha, amphiregulin, betacellulin, heparin-binding EGF and heregulin. These data suggest that human lung epith elial cells have the potential for multifactorial modulation of ErbB recept or family signalling through control of Ligand as well as receptor producti on. In this system, the probable importance of TGF alpha-stimulated signali ng for tumorigenicity is supported by its 13-fold higher production in tumo rigenic as compared with non-tumorigenic cells and the 2-fold or lower diff erences observed in production of the other epidermal growth factor (EGF) f amily ligands. (C) 1999 Published by Elsevier Science Ireland Ltd. All righ ts reserved.