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Characterization of Functional Type I Insulin-Like Growth Factor Receptors from Human Choriocarcinoma Cells^*

Department I of Obstetrics and Gynecology, University Central Hospital SF-00290 Helsinki
the Minerua Institute for Medical Research SF-02700 Kauniainen, Finland

Address all correspondence and requests for reprints to: Olli Ritvos, Hormone Laboratory, Departments of Obstetrics and Gynecology, University Central Hospital, Haartmaninkatu 2, SF-00290 Helsinki, Finland.

Abstract

Specific receptors for insulin-like growth factor I (IGF-I) on cultured human choriocarcinoma cells (JEG-3 and BeWo) were characterized. The binding of ¹²⁵I-labeled recombinant (Thr⁵⁹)IGF-I to the cells was reversible and time, temperature, and pH dependent. Steady state of binding occurred after 16 h at 4 C, pH 7.4. Natural human IGF-I (hlGF-I), hIGF-II, recombinant (N-Met)IGF-I, rat multiplication-stimulating activity, and insulin were 200%, 37%, 37%, 1.6%, and 0.1% as potent as (Thr89)IGF-I in inhibiting the binding of [¹²⁵I]iodo- (Thr69)IGF-I to JEG-3 cells, respectively. Epidermal growth factor was ineffective. The half-maximal displacement of [¹²⁵I] iodo-(Thr⁵⁹)IGF-I by unlabeled (Thr89)IGF-I occurred at 11 ± 2 ng/ml (mean ± SEM) in both JEG-3 and BeWo cells. Scatchard analysis of the competitive binding data revealed linear plots indicating a single species of binding sites with an association constant of 0.8 x 10⁹ M^-1 for the binding of [¹²⁵I]iodo-(Thr69)IGFI to both cell lines. The binding capacity was 30,000 and 20,000 sites/cell for JEG-3 and BeWo cells, respectively. Chemical cross-linking of [¹²⁵I]iodo-(Thr⁵⁹)IGF-I to JEG-3 cells revealed two receptor complexes of 130K and 260K. Their formation was completely inhibited by an excess of unlabeled (Thr⁵⁹)IGF-I or hIGF-II. Increasing amounts of insulin affected both labeled bands equally, suggesting that the 130K and 260K bands represent the monomer and dimer forms, respectively, of the ligandbinding -subunit of type I IGF receptor. (Thr⁵⁹)IGF-I, in a dose-dependent manner, stimulated uptake of nonmetabolizable -[³H]aminoisobutyric acid by JEG-3 cells, showing that the receptor is biologically active.

Our results demonstrate that choriocarcinoma cells possess functional high affinity type I IGF receptors and suggest that IGF-I is involved in the growth-regulating processes of JEG-3 and BeWo cells. These cells may provide a useful model to study the role of IGFs in trophoblast physiology. (Endocrinology 122: 395–401, 1988)

Footnotes

^* This work was supported by grants from the Ida Montin and Paulo Foundations and the Cancer Society of Finland.

Received May 13, 1987.

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