Transforming growth factor-α acts as an autocrine growth factor in ovarian carcinoma cell lines

The potential of transforming growth factor-alpha (TGF-alpha) to function as an autocrine growth factor was evaluated in numerous ovarian carcinoma cell lines. All 17 lines which were examined expressed the epidermal growth factor receptor and 16 cell lines, in addition, concomitantly secreted TGF-alpha. Radioimmunoassay of processed serum-free-conditioned medium indicated TGF-alpha concentrations ranging from 16 to 197 pg/ml, or 1.5 to 95 ng/10(8) cells. 125I-TGF-alpha bound to a single class of high-affinity-binding sites on the surface of the cells. The dissociation constant for the 125I-TGF-alpha/epidermal growth factor receptor complex ranged from 0.21 to 5.3 nM with receptor numbers from 3,500 to 96,000/cell, depending upon the cell line. The growth of 8 ovarian cell lines was stimulated in a dose-dependent manner when grown in the presence of exogenous TGF-alpha. Growth in 4 of 5 cell lines capable of serum-free propagation was inhibited from 28 to 56% when cultured in medium containing a TGF-alpha-neutralizing monoclonal antibody. These results support the view that TGF-alpha is an autocrine growth factor for cell lines derived from ovarian cancers of epithelial origin and suggest a potential role for TGF-alpha in the pathogenesis or progression of the disease.