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Regolation of neuroblastoma cell growth by IGF-I

IGF-I 对神经母细胞瘤细胞生长的调节

基本信息

批准号：
10671669
负责人：
WASA Masafumi
金额：
$ 1.66万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671669/
关键词：
neuroblastoma IGF-I Glutamine amino acid transport 小児悪性腫瘍

项目摘要

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.

目前尚不清楚胰岛素样生长因子-I（IGF-I）如何在关键营养素（如谷氨酰胺）有限的条件下调节癌细胞生长。我们研究了IGF-I对谷氨酰胺缺乏的人神经母细胞瘤细胞系SK-N-SH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，测定细胞生长和^3H-氨基酸转运。细胞生长速率依赖于谷氨酰胺浓度。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谷氨酰胺中无此作用。在2 mM和100 μM谷氨酰胺中，IGF-I处理的细胞中^3H-胸苷和^3H-亮氨酸掺入量均显著增加。在针对I型IGF受体（IGF-IR）的单克隆抗体的存在下，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相互作用刺激细胞生长，通过增加氨基酸转运在低谷氨酰胺水平的条件下，在人神经母细胞瘤细胞系。这种机制可能允许即使在营养缺乏的肿瘤组织中也能维持细胞生长。