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.

Abstract

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) in the growth and development of these tumors. Specific binding 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 chemical cross-linking studies. Binding studies with 125I-insulin, 125I-IGF-I, and 125I-IGF-II revealed the presence of specific binding sites for these three growth factors. Specificity studies revealed 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 analysis of the binding data revealed that the cell line has a higher number of IGF-II receptor (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 cell number and incorporation of [3H] thymidine into the DNA of the cells. Insulin-like growth factor-II was potent in stimulating the growth of these cells, but IGF-I did not have any effect. Insulin stimulated DNA synthesis only at pharmacologic concentrations. These results indicate that IGF-II is mitogenic to mixed mesodermal tumors of the uterus. Insulin-like growth factor II may be involved in the growth regulation of mixed mesodermal tumors of the uterus.