Insulin-like growth factor-I stimulates amino acid transport in a glutamine-deprived human neuroblastoma cell line

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 a glutamine-deprived human neuroblastoma cell line, SK-N-SH. Cell growth was measured, and H-3-labeled amino acid transport was assayed after treatment with or without IGF-I (50 ng/ml) in 2 mM (control) and 100 muM glutamine concentrations. Cell growth rates were dependent on glutamine concentrations. IGF-I stimulated cell growth in both 2 mM and 100 muM glutamine. IGF-I stimulated glutamine transport in 100 muM glutamine with the mechanism of increasing carrier V-max,but had no effect in 2 mM glutamine. IGF-I also stimulated leucine, glutamate and 2-(methylamino)isobutyric acid transport in 100 muM glutamine. There were significant increases in [H-3]thymidine and [H-3]leucine incorporation in IGF-I-treated cells in both 2 mM and 100 muM glutamine. These data suggest that IGF-I 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 nutrient-deprived tumor tissues. (C) 2001 Elsevier Science B.V. All rights reserved.