title: Modulation of insulin-like growth factor (IGF) action by IGF-binding proteins in normal, benign, and malignant smooth muscle tissues.
abstract: The insulin-like growth factor (IGF) system is involved in the growth of uterine leiomyomas (L), as these tumors have higher IGF-II messenger ribonucleic acid levels, type I IGF receptor levels, and IGF-I peptide concentrations than myometrium (M). Furthermore, cultured L smooth muscle cells (SMC) respond with greater efficiency to IGF-I than M SMC. Here we investigate a possible modulating role of the binding proteins for the IGFs (IGFBPs) on the actions of IGFs. IGFBP-3 is the most predominant IGFBP in conditioned medium from SMC, with levels ranging from 13-288 ng/mL. Incubation of SMC cultures with IGF-I and the IGF-I analogs long-R3IGF-I and des(1-3)-IGF-I, which have decreased affinity for IGFBPs, revealed a facilitating effect of IGFBPs on the growth-stimulating activity of a high concentration of IGF-I in cell lines with high IGFBP-3 levels. Both a decreased level of IGFBP-3 and a low concentration of the growth factors added were a disadvantage for the facilitating effect. In M and L tissue sections, IGFBP-3 was found exclusively bound to the constituting cells, not in the extracellular matrix. This suggests that a negative modulating role of IGFBP-3 due to sequestration of IGF-I, as occurs in culture medium, is less relevant in vivo. In leiomyosarcoma sections, IGFBP-3 levels are decreased, indicating a decreasing, role for this binding protein in malignant smooth muscle tissues.
authors.affiliation: Department of Pathology, University Hospital Utrecht, The Netherlands. leoven@knoware.nl
authors.forename: L T
authors.initials: LT
authors.lastname: van der Ven
authors.forename: S C
authors.initials: SC
authors.lastname: Van Buul-Offers
authors.forename: T
authors.initials: T
authors.lastname: Gloudemans
authors.forename: R J
authors.initials: RJ
authors.lastname: Bloemen
authors.forename: P J
authors.initials: PJ
authors.lastname: Roholl
authors.forename: J S
authors.initials: JS
authors.lastname: Sussenbach
authors.forename: W
authors.initials: W
authors.lastname: Den Otter
mesh_terms: D000328:Adult; D000368:Aged; D002455:Cell Division; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis / Q000502:physiology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007889:Leiomyoma / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology*; D014594:Uterine Neoplasms / Q000473:pathology*
chemical_list: D017077:Culture Media, Conditioned; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I