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.
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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)
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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
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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
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