title: In vivo treatment with antibody against IGF-1 receptor suppresses growth of human rhabdomyosarcoma and down-regulates p34cdc2.
abstract: In a previous study, we have shown that insulin-like growth factor type 2 (IGF-2) functions as an autocrine growth factor in human rhabdomyosarcoma (RMS) cell lines. In addition, we demonstrated that the inhibition of binding of IGF-2 to the IGF-1 receptor, mediated by suramin, blocked the growth of RMS cells in vitro. We now report that, in vivo, a specific IGF-1 receptor blocking antibody (alpha IR-3), but not suramin, suppresses RMS tumor growth. Both progression of tumor growth in tumor-bearing animals and formation of newly established tumors were suppressed by treatment with alpha IR-3. Histological analysis of tumors from treated animals did not reveal necrotic lesions, implying that the treatments had no cytotoxic effect. The decrease in tumor growth was associated with a decrease of p34cdc2, a cellular protein involved in cell cycle regulation, suggesting that treatment resulted in the arrest of cellular proliferation. We speculate, therefore, that agents which block the IGF signaling pathway may find application in treatment of RMS.
authors.affiliation: Molecular Oncology Section, National Cancer Institute, Bethesda, Maryland 20892-1928.
authors.forename: T
authors.initials: T
authors.lastname: Kalebic
authors.forename: M
authors.initials: M
authors.lastname: Tsokos
authors.forename: L J
authors.initials: LJ
authors.lastname: Helman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002455:Cell Division; D015536:Down-Regulation; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D018233:Rhabdomyosarcoma, Embryonal / Q000378:metabolism / Q000473:pathology*; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D013498:Suramin; D017526:Receptor, IGF Type 1; D016203:CDC2 Protein Kinase