IGF-binding protein-6 is involved in growth inhibition in SH-SY5Y human neuroblastoma cells: its production is both IGF- and cell density-dependent

• Published in: Journal of endocrinology Vol. 152; no. 2; pp. 221 - 227
• Main Authors: BABAJKO, S, LENEUVE, P, LORET, C, BINOUX, M
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01.02.1997; Portland Press
• Subjects: Biological and medical sciences; Blotting, Western; Cell Count; Cell Division - drug effects; Cell Division - physiology; Feedback; Fibroblast Growth Factor 1 - pharmacology; Fibroblast Growth Factor 2 - pharmacology; General aspects (metabolism, cell proliferation, established cell line...); Humans; Immunoblotting; Insulin - pharmacology; Insulin-Like Growth Factor Binding Protein 6 - metabolism; Insulin-Like Growth Factor I - pharmacology; Insulin-Like Growth Factor II - pharmacology; Medical sciences; Nerve Growth Factors - pharmacology; Neuroblastoma - metabolism; Neuroblastoma - pathology; Somatomedins - metabolism; Tumor cell; Tumor Cells, Cultured; Tumors; Human; Insulin like growth factor; Cell line; Growth; Insulin growth factor binding protein; Tumor; Neuroblastoma; Autonomic neuropathy; Differentiation; Gene expression; In vitro
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/joe.0.1520221

Abstract The IGF system is involved in the growth and differentiation of neuroblastoma cells, but the precise roles played by the IGF-binding proteins (IGFBPs) remain unknown. We have examined the expression and functions of IGFBPs produced by the neuroblastoma cell line, SHSY5Y, in the presence of: insulin, IGF-I, IGF-II, des(1–3)IGF-I (an IGF-I analogue with weak affinity for IGFBPs), acidic fibroblast growth factor, basic fibroblast growth factor, or nerve growth factor. Under basal conditions, SH-SY5Y cells in serum-free medium secreted IGF-II, and traces of IGF-I, IGFBP-2 and IGFBP-4. After 24 h of culture, comparative mitogenic potencies were: des(1–3)IGF-I>IGF-1>IGF-II>insulin. After 48 h, when IGFBP-2 and IGFBP-4 concentrations in the culture media had increased, des(1–3)IGF-I remained the most active, but the activity of insulin now equalled or exceeded that of IGF-I and IGF-II. This suggests a negative feedback mechanism involving partial sequestration of IGF-I and IGF-II by IGFBP-2 and IGFBP-4. At high cell density and with high concentrations of IGF-I, des(1–3)IGF-I (40 ng/ml) or IGF-II (80 ng/ml), the mitogenic activities of the IGFs diminished concomitantly with the appearance in the culture medium of an additional IGFBP identified as IGFBP-6, whose production depended on activation of the type 1 IGF receptor. These findings suggest that IGFBP-6 contributes as an autocrine inhibitor in the regulation of growth by the IGF system in these neuroblastoma cells. Journal of Endocrinology (1997) 152, 221–227