Binding of Insulin-like Growth Factors to Tera-2 Human Embryonal Carcinoma Cells during Differentiation

James F. Fleck, George W. Sledge, Sue V. Benenati, Charles A. Frolik, Bruce J. Roth, Kenneth S. Hirsch

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Differentiation of Tera-2 human embryonal carcinoma cells by exposure to 2.1 mM α-difluoromethylornithine resulted in changes in morphology, a decrease in growth rate, and changes in the expression of SSEA-1 differentiation antigen. While the binding of 125I-insulin-like growth factor I (IGF-I) remained relatively constant during differentiation, binding of 125I-IGF-II increased 2–3-fold. Further, the binding of IGF-II was 87 times greater than IGF-I in both undifferentiated and differentiated ceUs. Undifferentiated Tera-2 cells exhibited a single class of binding sites for both IGF-I (KD = 1.2 nM, 7.0 × 103 sites/cell) and IGF-II (KD = 83 nM, 3.4 x 10s sites/cell). Following differentiation, IGF-I continued to bind to a single class of binding sites (KD 1.0 nM, 6.7 × 103 sites/cell) whereas IGF-II bound to both high-affinity sites (KDH 03 nM, 2.2 × 105 sites/cell) and low-affinity sites (KDL 15.1 nM, 1.6 x 107 sites/ceU). The binding of iodinated IGF-II was blocked by unlabeled IGF-II but not IGF-I. In contrast, 125I-IGF-I binding was prevented by either IGF-I or IGF-II. Affinity cross-linking experiments demonstrated the presence of both type I and type II IGF receptors along with a number of IGF binding proteins. IGF-I failed to stimulate the incorporation of [3H]thymidine in both undifferentiated and differentiated cells. Although IGF-II caused a significant increase in [3H]thymidine incorporation in both undifferentiated and differentiated Tera-2 cells, the magnitude of the response and the sensitivity of the cells to IGF-II stimulation was diminished following differentiation. The observed changes in IGF-II binding, which occur in conjunction with cellular differentiation, may be an important feature of the expression of the differentiated phenotype by human germ cell tumors.

Original languageEnglish
Pages (from-to)4395-4401
Number of pages7
JournalCancer research
Volume51
Issue number16
StatePublished - Aug 15 1991
Externally publishedYes

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    Fleck, J. F., Sledge, G. W., Benenati, S. V., Frolik, C. A., Roth, B. J., & Hirsch, K. S. (1991). Binding of Insulin-like Growth Factors to Tera-2 Human Embryonal Carcinoma Cells during Differentiation. Cancer research, 51(16), 4395-4401.