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Suramin Inhibits the Growth of Human Rhabdomyosarcoma by Interrupting the Insulin-like Growth Factor II Autocrine Growth Loop

Molecular Genetics Section, Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892

Suramin is a polysulfonated naphthylurea with antineoplastic activity that binds various peptide growth factors. Since we previously demonstrated that insulin-like growth factor II (IGF-II) is an autocrine growth factor in human rhabdomyosarcoma (RMS), we studied the effect of suramin on the growth of human RMS cells. Suramin caused a dose-dependent decrease of RMS cell number grown either in 10% fetal bovine serum or in serum-free medium (half-maximal effective dose in mitogenic assays, 1.6 x 10^–4 and 9 x 10^–5 M, respectively). IGF-II and IGF-I added to RMS cells in the presence of suramin reversed the suramin-induced inhibition of cell growth. Since IGF-II exerts its mitogenic effects on RMS cells by binding to the type I receptor, we performed radioreceptor assays using ¹²⁵I-IGF-I and found that suramin displaced ¹²⁵I-IGF-I from the type I IGF receptor. There was an excellent correlation between the doses of suramin effective in inhibiting the growth of RMS cells and those that displaced the binding of IGF-I. Our data indicate that suramin exerts its effect on RMS cell growth by interfering with the binding of IGF-II to the type I IGF receptor, thereby interrupting the IGF-II autocrine growth in these cells. Disrupting autonomous growth of RMS may be a promising novel therapeutic approach.

¹ To whom requests for reprints should be addressed, at Molecular Genetics Section, Pediatric Branch, National Cancer Institute, Building 10, Room 13N240, Bethesda, MD 20892.

Received 8/28/91. Accepted 1/24/92.

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