INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEIN PRODUCTION IN HUMAN FOLLICULAR THYROID-CARCINOMA CELLS

IGFs and IGF binding proteins (IGFBPs) appear to serve as regulators o f non-malignant thyroid cells from several species, but little is know n about their role in thyroid malignancy. We have examined IGFBP produ ction and hormonal regulation in two human thyroid follicular carcinom a cell lines; FTC-133 line derived from a local tumor recurrence and F TC-236 cells from a tumor metastasis. Under basal conditions these cel l 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 E GF or TPA. IGFBP-4 production was increased in the presence of TSH, fo rskolin, 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 increase d in the presence of TSH, EGF, and forskolin. These results indicate t hat IGFBP production in human thyroid follicular carcinoma clones is u nder 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 far these peptides in modulating malignant thyroid growth.