Insulin-like growth factor binding protein production in human follicular thyroid carcinoma cells

IGFs and IGF binding proteins (IGFBPs) appear to serve as regulators of non-malignant thyroid cells from several species, but little is known about their role in thyroid malignancy. We have examined IGFBP production and hormonal regulation in two human thyroid follicular carcinoma cell lines; FTC-133 line derived from a local tumor recurrence and FTC-236 cells from a tumor metastasis. Under basal conditions these cell lines produced IGFBP-3, IGFBP-4 and IGFBP-2. In both cell lines, EGF or TPA stimulated IGFBP-3 production while TSH or forskolin inhibited IGFBP-3 production and reduced the stimulation of IGFBP-3 seen with EGF or TPA. IGFBP-4 production was increased in the presence of TSH, forskolin, and EGF and was reduced by TPA. mRNA assessment revealed that IGFBP-3 mRNA, more abundant in FTC-236 than FTC-133 cells, increased in the presence of EGF or TPA, while IGFBP-4 mRNA content was increased in the presence of TSH, EGF, and forskolin. These results indicate that IGFBP production in human thyroid follicular carcinoma clones is under specific hormonal regulation. IGFBP-3 production is increased by dedifferentiation factors such as EGF and TPA and inhibited by TSH and forskolin, which enhance differentiated function. The highly specific regulation of IGFBP-3 and IGFBP-4 suggests a potential role for these peptides in modulating malignant thyroid growth.