Since the TT human medullary thyroid carcinoma cell line required fewer exogenous growth factors (serum), we investigated whether this line has an autocrine mechanism by examining the effects of antibodies directed toward insulin-like growth factor I (IGF-I) and its receptor on TT cell growth in serum-free conditions. Treating cells with anti-IGF-I antibody for four days reduced the cell number by more than 50% compared with a nonimmune IgG control. Furthermore, a monoclonal antibody to the IGF-I receptor suppressed DNA synthesis when determined by a [3H]thymidine incorporation assay. Exogenous IGF-I (20 ng/mL) stimulated [3H]thymidine incorporation in serum-free medium; approximately 70% of the IGF-I-induced stimulation was blocked by the presence of the receptor antibody. Treating TT cells with IGF-I for 48 hours increased the cell population in the S phase by 62% when analyzed by flow cytometry. These data suggest that TT cells might respond to endogenously produced IGF-I and therefore provide an in vitro model for autocrine regulation of human tumor cell growth by IGF-I.
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