Epidermal growth factor (EGF)- and transforming growth factor alpha-stimulated invasion and growth of follicular thyroid cancer cells can be blocked by antagonism to the EGF receptor and tyrosine kinase in vitro
Hölting T, Siperstein AE, Clark OH, Duh Q-Y. Epidermal growth factor (EGF)- and transforming growth factor alpha-stimulated invasion and growth of follicular thyroid cancer cells can be blocked by antagonism to the EGF receptor and tyrosine kinase in vitro. Eur J Endocrinol 1995;132:229–35. ISSN 0804–4643 We have shown recently that epidermal growth factor (EGF) enhanced invasion and growth of differentiated thyroid cancer cells in vitro and in vivo. The present study analyzed the effects of transforming growth factor alpha (TGF-α) on invasion and growth of a follicular thyroid cancer cell line (FTC133) and whether blocking the EGF receptor by a monoclonal antibody (Mab528) or blocking the tyrosine kinase of the receptor by genistein abolished the EGF- and TFG-α-mediated effects. Growth and invasion (penetration of 8-μm pore polycarbonate membranes coated with Matrigel) were determined by the dimethylthiazol-diphenyltetrazolium bromide assay. Epidermal growth factor (10 ng/l) stimulated invasion of FTC133 by 42% and TGF-α (10 ng/l) stimulated invasion of FTC133 by 27% (p < 0.02). Both growth factors also enhanced growth by 62% (EGF) and 30% (TGF-α) (p < 0.003). Epidermal growth factor receptor antibodies (1 μg/ml) abolished EGF-mediated stimulation of invasion and growth completely and that of TGF-α by 93%. At 100 ng/ml genistein reversed EGF and TGF-α stimulation, and at 1 μg/ml it inhibited invasion (27%) and growth (40%) of unstimulated FTC133 (p < 0.02). We conclude that TGF-α stimulates invasion and growth of follicular thyroid cancer by binding to the EGF receptors, that EGF- and TGF-α-mediated effects can be blocked by antagonism to the EGF receptor and to tyrosine kinase, and that genistein not only neutralized EGF and TGF-α effects but also inhibited invasion and growth of unstimulated FTC133. Therefore, tyrosine kinase activity via other signalling systems must be crucial for basal invasion and growth of follicular thyroid cancer cells in culture. Thomas Hölting, Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany