Amino acid transport in a human neuroblastoma cell line is regulated by the type I insulin-like growth factor receptor

Abstract

Insulin-like growth factor I (IGF-I) and IGF-II stimulate cancer cell proliferation via interaction with the type I IGF receptor (IGF-IR). We put forward the hypothesis that IGF-IR mediates cancer cell growth by regulating amino acid transport, both when sufficient nutrients are present and when key nutrients such as glutamine are in limited supply. We examined the effects of αIR3, the monoclonal antibody recognizing IGF-IR, on cell growth and amino acid transport across the cell membrane in a human neuroblastoma cell line, SK-N-SH. In the presence of αIR3 (2 μg/ml), cell proliferation was significantly attenuated in both control (2 mM glutamine) and glutamine-deprived (0 mM glutamine) groups. Glutamine deprivation resulted in significantly increased glutamate (system X AG -), MeAIB (system A), and leucine (system L) transport, which was blocked by αIR3. Glutamine (system ASC) and MeAIB transport was significantly decreased by αIR3 in the control group. Addition of αIR3 significantly decreased DNA and protein biosynthesis in both groups. Glutamine deprivation increased the IGF-IR protein on the cell surface. Our results suggest that activation of IGF-IR promotes neuroblastoma cell proliferation by regulating trans-membrane amino acid transport.