Insulin-like growth factor (IGF) binding protein from human decidua inhibits the binding and biological action of IGF-I in cultured choriocarcinoma cells
O RITVOS, T RANTA, J JALKANEN… - …, 1988 - academic.oup.com
O RITVOS, T RANTA, J JALKANEN, AM SUIKKARI, R VOUTILAINEN, H BOHN…
Endocrinology, 1988•academic.oup.comThe placenta expresses genes for insulin-like growth factors (IGFs) and possesses IGF-
receptors, suggesting that placental growth is regulated by IGFs in an autocrine manner. We
have previously shown that human decidua, but not placenta, synthesizes and secretes a 34
K IGF-binding protein (34 K IGF-BP) called placental protein 12. We now used human
choriocarcinoma JEG-3 cell monolayer cultures and recombinant (Thr59) IGF-I as a model to
study whether the decidual 34 K IGF-BP is able to modulate the receptor binding and …
receptors, suggesting that placental growth is regulated by IGFs in an autocrine manner. We
have previously shown that human decidua, but not placenta, synthesizes and secretes a 34
K IGF-binding protein (34 K IGF-BP) called placental protein 12. We now used human
choriocarcinoma JEG-3 cell monolayer cultures and recombinant (Thr59) IGF-I as a model to
study whether the decidual 34 K IGF-BP is able to modulate the receptor binding and …
The placenta expresses genes for insulin-like growth factors (IGFs) and possesses IGF-receptors, suggesting that placental growth is regulated by IGFs in an autocrine manner. We have previously shown that human decidua, but not placenta, synthesizes and secretes a 34 K IGF-binding protein (34 K IGF-BP) called placental protein 12. We now used human choriocarcinoma JEG-3 cell monolayer cultures and recombinant (Thr59)IGF-I as a model to study whether the decidual 34 K IGF-BP is able to modulate the receptor binding and biological activity of IGFs in trophoblasts. JEG-3 cells, which possess type I IGF receptors, were unable to produce IGF-BPs. Purified 34 K IGF-BP specifically bound [125I]iodo-(Thr59)IGFI. Multiplication-stimulating activity had 2.5% the potency of (Thr59)IGF-I, and insulin had no effect on the binding of [125I] iodo-(Thr59)IGF-I. 34 K IGF-BP inhibited the binding of [125I] iodo-(ThrS9)IGF-I to JEG-3 monolayers in a concentration-dependent manner by forming with the tracer a soluble complex that could not bind to the cell surface as demonstrated by competitive binding and cross-linking experiments. After incubating the cell monolayers with [125I]iodo-(ThrB9)IGF-I in the presence of purified binding protein, followed by cross-linking, no affinity labeled bands were seen on autoradiography. In contrast, an intensely labeled band at 40 K was detected when the incubation medium was analyzed, suggesting that (Thr59)IGF-I and 34 K IGF-BP formed a complex in a 1:1 molar ratio. Also, 34 K IGF-BP inhibited both basal and IGF-I-stimulated uptake of α-[3H]aminoisobutyric acid in JEG-3 cells. RNA analysis revealed that IGF-II is expressed in JEG-3 cells.
We conclude that decidual 34 K IGF-BP inhibits the cellular binding and biological action of IGFs in JEG-3 cells. Our data show that JEG-3 cells represent a cell type that can produce IGF, but not IGF-BPs. These cells may thus provide a useful model system for a better understanding of autocrine growth regulation mediated by the IGFs. (Endocrinology122: 2150–2157,1988)
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