SPECIFIC RECEPTORS AND GROWTH EFFECTS OF INSULIN AND INSULIN-LIKE GROWTH-FACTORS IN A HUMAN CELL-LINE DERIVED FROM MIXED MESODERMAL TUMOR OF THE UTERUS

OBJECTIVE: Mixed mesodermal tumors of the uterus are highly malignant. The purpose of our present study was to investigate possible roles of insulin and insulin-like growth factors I and II (IGF-I and IGF-II) i n the growth and development of these tumors. METHODS: Specific bindin g and growth effects of insulin, IGF-I, and IGF-II were studied in SK- UT-1 cells, derived from a human mixed mesodermal tumor of the uterus. The receptors were further characterized by competitive binding and c hemical cross-linking studies, RESULTS: Binding studies with I-125-ins ulin, I-125-IGF-I, and I-125-IGF-II revealed the presence of specific binding sites for these three growth factors. Specificity studies reve aled that the binding sites for IGF-I and IGF-II are distinct. Binding of IGF-II was much higher than insulin and IGF-I binding. Scatchard a nalysis of the binding data revealed that the cell line has a higher n umber of IGF-II receptors (100,000 sites per cell) than insulin (1400 sites per cell) and IGF-1 (1200 sites per cell) receptors. The effect of these growth factors on cell growth was studied by monitoring the c ell number and incorporation of [H-3] thymidine into the DNA of the ce lls. Insulin-like growth factor-II was potent in stimulating the growt h of these cells, but IGF-I did not have any effect. Insulin stimulate d DNA synthesis only at pharmacologic concentrations. CONCLUSION: Thes e results indicate that IGF-II is mitogenic to mixed mesodermal tumors of the uterus. Insulin-like growth factor II may be involved in the g rowth regulation of mixed mesodermal tumors of the uterus.