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 3H-labeled amino acid transport was assayed after treatment with or without IGF-I (50 ng/ml) in 2 mM (control) and 100 microM glutamine concentrations. Cell growth rates were dependent on glutamine concentrations. IGF-I stimulated cell growth in both 2 mM and 100 microM glutamine. IGF-I stimulated glutamine transport in 100 microM glutamine with the mechanism of increasing carrier Vmax, but had no effect in 2 mM glutamine. IGF-I also stimulated leucine, glutamate and 2-(methylamino)isobutyric acid transport in 100 microM glutamine. There were significant increases in [3H]thymidine and [3H]leucine incorporation in IGF-I-treated cells in both 2 mM and 100 microM 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.