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

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, SH-SY5Y, 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-I > 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.

• Authors: S Babajko, P Leneuve, C Loret, M Binoux
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 152 Issue 2 Pg. 221-7 (Feb 1997) ISSN: 0022-0795 [Print] England
• PMID: 9071979 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• Insulin-Like Growth Factor Binding Protein 6
• Nerve Growth Factors
• Somatomedins
• Fibroblast Growth Factor 2
• Fibroblast Growth Factor 1
• Insulin-Like Growth Factor I
• Insulin-Like Growth Factor II

Topics

• Blotting, Western
• Cell Count
• Cell Division (drug effects, physiology)
• Feedback
• Fibroblast Growth Factor 1 (pharmacology)
• Fibroblast Growth Factor 2 (pharmacology)
• Humans
• Immunoblotting
• Insulin (pharmacology)
• Insulin-Like Growth Factor Binding Protein 6 (metabolism)
• Insulin-Like Growth Factor I (pharmacology)
• Insulin-Like Growth Factor II (pharmacology)
• Nerve Growth Factors (pharmacology)
• Neuroblastoma (metabolism, pathology)
• Somatomedins (metabolism)
• Tumor Cells, Cultured