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

Caterina P. Minniti, Mario Maggi, Lee J. Helman

Research output: Contribution to journalArticle

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Abstract

Suramin is a poiysulfonated 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 l25I-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.

Original languageEnglish (US)
Pages (from-to)1830-1835
Number of pages6
JournalCancer Research
Volume52
Issue number7
StatePublished - 1992
Externally publishedYes

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Suramin
Insulin-Like Growth Factor II
Rhabdomyosarcoma
Growth
Insulin-Like Growth Factor I
IGF Type 1 Receptor
Intercellular Signaling Peptides and Proteins
Radioligand Assay
Serum-Free Culture Media
Antineoplastic Agents
Cell Count
Peptides

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Suramin Inhibits the Growth of Human Rhabdomyosarcoma by Interrupting the Insulin-like Growth Factor II Autocrine Growth Loop. / Minniti, Caterina P.; Maggi, Mario; Helman, Lee J.

In: Cancer Research, Vol. 52, No. 7, 1992, p. 1830-1835.

Research output: Contribution to journalArticle

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