Babajko S, Leneuve P, Loret C, Binoux M
Institut National de la Santé et de la Recherche Médicale, Unité de Recherches sur la Régulation de la Croissance (U.142), Hôpital Saint Antoine, Paris, France.
J Endocrinol. 1997 Feb;152(2):221-7. doi: 10.1677/joe.0.1520221.
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.
胰岛素样生长因子（IGF）系统参与神经母细胞瘤细胞的生长和分化，但IGF结合蛋白（IGFBP）所起的确切作用尚不清楚。我们研究了神经母细胞瘤细胞系SH-SY5Y在以下物质存在的情况下产生的IGFBP的表达和功能：胰岛素、IGF-I、IGF-II、des(1-3)IGF-I（一种对IGFBP亲和力较弱的IGF-I类似物）、酸性成纤维细胞生长因子、碱性成纤维细胞生长因子或神经生长因子。在基础条件下，无血清培养基中的SH-SY5Y细胞分泌IGF-II以及痕量的IGF-I、IGFBP-2和IGFBP-4。培养24小时后，促有丝分裂效力比较结果为：des(1-3)IGF-I > IGF-I > IGF-II > 胰岛素。48小时后，当培养基中IGFBP-2和IGFBP-4浓度增加时，des(1-3)IGF-I仍然最具活性，但胰岛素的活性此时等于或超过了IGF-I和IGF-II。这表明存在一种负反馈机制，涉及IGFBP-2和IGFBP-4对IGF-I和IGF-II的部分隔离。在高细胞密度以及高浓度的IGF-I、des(1-3)IGF-I（40 ng/ml）或IGF-II（80 ng/ml）条件下，IGF的促有丝分裂活性降低，同时培养基中出现了另一种被鉴定为IGFBP-6的IGFBP，其产生依赖于1型IGF受体的激活。这些发现表明，在这些神经母细胞瘤细胞中，IGFBP-6作为一种自分泌抑制剂参与IGF系统对生长的调节。
