title: Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits breast cancer cell motility.
abstract: The breast cancer malignant phenotype is regulated by steroid hormones and peptide growth factors. We have shown previously that insulin-like growth factor-I (IGF-I) stimulates cell motility in a metastatic cell line, MDA-231BO. In this study, we show that neutralization of IGF action by a type I IGF receptor (IGFR1) blocking antibody or neutralization of IGF-I by IGFBP-1 reduced cell motility. However, in addition to inhibiting IGF effects, IGFBP-1 also diminished basal motility. Because IGFBP-1 contains a RGD motif important in binding of fibronectin to its alpha 5 beta 1 integrin receptor, we examined the effect of inhibiting integrin function on cell motility. As expected, disruption of fibronectin-integrin interactions interrupted basal motility in MDA-231BO cells. In addition, disruption of integrin function by an alpha 5 beta 1 blocking peptide also inhibited IGF stimulation of cell motility. To determine whether integrin function could interfere with IGF signaling, we used an alpha 5 beta 1 blocking peptide to show that in MDA-231BO cells integrin occupancy appeared necessary for phosphorylation of insulin receptor substrate-2 but not for IGFR1 activation. We conclude that IGFR1 and integrin action are linked in these breast cancer cells as disruption of integrin binding to its receptor influences IGF signaling pathways. Moreover, IGFBP-1 could have dual effects on cancer cell motility by disrupting both receptor systems.
authors.affiliation: University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, USA.
authors.forename: Xihong
authors.initials: X
authors.lastname: Zhang
authors.forename: Douglas
authors.initials: D
authors.lastname: Yee
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D016023:Integrins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D009842:Oligopeptides / Q000494:pharmacology; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000906:Antibodies; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010750:Phosphoproteins; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; C094340:integrin alphavbeta1; D007334:Insulin-Like Growth Factor I; C047981:arginyl-glycyl-aspartic acid