An acid-stable insulin-like growth factor (IGF)-binding protein from pig serum inhibits binding of IGF-I and IGF-II to vascular endothelial cells

Abstract

The effects of a porcine insulin-like growth factor (IGF)-binding protein on binding of IGF-I and IGF-II to porcine aortic endothelial cells (PAEC) were determined. Binding of 125I-labelled IGF-I and -II to IGF receptors was inhibited by IGF-binding protein. IGF-binding protein inhibited binding of IGF-I and -II in a dose-dependent manner with half-maximal inhibition occurring at 5.43 and 108 micrograms/l respectively. A 125I-labelled IGF-I--IGF-binding protein complex, formed by incubating 125I-labelled IGF-I with IGF-binding protein overnight at 4 degrees C, did not effectively bind to endothelial IGF receptors. Addition of IGF-binding protein to PAEC previously incubated with IGF-I caused a marked dissociation of bound IGF-I (47% dissociation within 12h). These results indicate that the acid-stable IGF-binding protein which appears to be a part of the 150 kDa GH-dependent binding protein, blocks binding of IGF-I and -II by the IGF receptors and appears to exhibit a higher affinity for IGF-I than the endothelial type-I IGF receptor. The ramifications of this latter point with respect to transfer of circulating IGFs (bound to their IGF-binding proteins) across the vascular endothelium are not clear.

Role for membrane and secreted insulin-like growth factor-binding protein-2 in the regulation of insulin-like growth factor action in lung tumors

“…The inhibitory action of soluble IGFBP-2 on ligand-receptor interaction and IGF-induced DNA synthesis in NSCLC cell line MOR is consistent with the contention that secreted/exogenous IGFBPs can act as blocking agents preventing IGF association with cell surface receptors. Similar observations have been made for IGFBP-1 and IGFBP-3 which block the cell surface association of radiolabeled IGF-I and which can inhibit either cell proliferation and/or cell function in a variety of different cell types (21)(22)(23)(24).…”

Regulation of human dermal papilla cell production of insulin-like growth factor binding protein-3 by retinoic acid, glucocorticoids, and insulin-like growth factor-1

“…It must also be considered that the IGFAGFBP-3 complex may not produce the same response in all cell types. Previous results in other systems indicate that formation of this complex can enhance or reduce IGF activity in a cell type-dependent manner (Blum et al, 1989;Ernst and Rodan, 1990;Conover and Powell, 1991;Gopinath et al, 1989;Bicsak et al, 1990;De Mellow and Baxter, 1988).…”

“…IGFBPs are secreted proteins that are known to modulate the activity of IGFs. Depending upon the system, IGFBPs can increase or decrease the activity of IGFs (Blum et al, 1989;Ernst and Rodan, 1990;Conover and Powell, 1991;Gopinath et al, 1989;Bicsak et al, 1990 De Mellow andBaxter, 1988). In ectocervical epithelial cells IGFBP-3 inhibits the mitogenic effects of IGF1, presumably by forming a complex with and preventing IGFl from interacting with the transmembrane type I IGFl receptor (i.e., lowering the concentration of free IGF in the extracellular environment) (Andreatta-van Leyen et al, 1994;Hembree et al, 1994).…”

Intracellular Levels and Secretion of Insulin‐Like‐Growth‐Factor‐Binding Proteins in MCF‐7/6, MCF‐7/AZ and MDA‐MB‐231 Breast Cancer Cells

“…Some IGFBPs may occur as phosphorylated or non-phosphorylated forms [lo]. It has been suggested that, according to their type or form, the IGFBPs can stimulate or inhibit the actions of IGFs by interfering with their binding to IGF receptors [ 11,121. It is therefore generally believed that the production of IGFBPs by cancer cells is of great importance and controls the regulation of cell proliferation, and of tumor growth, by the IGFs and the IGF-I receptor [8].…”