Regolation of neuroblastoma cell growth by IGF-I

在谷氨酰胺等关键营养素供应有限的情况下，胰岛素样生长因子-I (IGF-I) 如何调节癌细胞生长仍不清楚。我们研究了 IGF-I 对谷氨酰胺剥夺的人神经母细胞瘤细胞系 SK-N-SH 中细胞生长和氨基酸转运的影响。在 2 mM（对照）和 100 μM 谷氨酰胺浓度下，用或不用 IGF-I (50 ng/ml) 处理后，测量了细胞生长，并测定了^3H-氨基酸转运。细胞生长速率取决于谷氨酰胺浓度。 IGF-I 在 2 mM 和 100 μM 谷氨酰胺中均刺激细胞生长。 IGF-I 在 100 μM 谷氨酰胺中刺激谷氨酰胺转运，其机制是增加载体 Vmax，但在 2 mM 谷氨酰胺中没有影响。在 2 mM 和 100 μM 谷氨酰胺中，IGF-I 处理的细胞中^3H-胸苷和^3H-亮氨酸掺入显着增加。在存在针对 I 型 IGF 受体 (IGF-IR) 的单克隆抗体的情况下，细胞增殖显着减弱，谷氨酰胺转运减少。这些数据表明，IGF-I/IGF-IR相互作用通过在人神经母细胞瘤细胞系中低谷氨酰胺水平的条件下增加氨基酸转运来刺激细胞生长。这种机制甚至可以在营养缺乏的肿瘤组织中维持细胞生长。

It is still unknown how insulin-like growth factor-I (IGF-I) regulates cancer cell growth in the condition of the limited availability of key nutrients, such as glutamine. We investigated the effects of IGF-I on cell growth and amino acid transport in aglutamine-deprived human neuroblastoma cell line, SK-N-SH.Cell growth was measured, and ^3H-amino acid transport was assayed after treatment with or without IGF-I (50 ng/ml) in 2 mM (control) and 100 μM glutamine concentrations. Cell growth rates were dependent on glutamine concentrations. IGF-I stimulated cell growth in both 2 mM and 100 μM glutamine. IGF-I stimulated glutamine transport in 100 μM glutamine with the mechanism of increasing carrier Vmax, but had no effect in 2 mM glutaunine There were significant increases in ^3H-thymidine and ^3H-leucine incorporation in IGF-I treated cells in both 2 mM and 100 μM glutamine. In the presence of the monoclonal antibody against the type I IGF receptor (IGF-IR), cell proliferation was significantly attenuated and glutamine transport was decreased. These data suggest that IGF-I/IGF-IR interaction stimulates cell growth by increasing amino acid transport in the condition of low glutamine levels in a human neuroblastoma cell line. This mechanism may allow to maintain cell growth even in nutrients-deprived tumor tissues.