Amino acid transport in a human neuroblastoma cell line is regulated by the type I insulin-like growth factor receptor.
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 alphaIR3, 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 alphaIR3 (2 micro/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 alphaIR3. Glutamine (system ASC) and MeAIB transport was significantly decreased by alphaIR3 in the control group. Addition of alphaIR3 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.
Wang
Hong-Sheng
HS
Department of Pediatric Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Osaka, Japan.
Wasa
Masafumi
M
Okada
Akira
A
D000596:Amino Acids / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D005434:Flow Cytometry; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D017526:Receptor, IGF Type 1 / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D000911:Antibodies, Monoclonal; D011506:Proteins; D005973:Glutamine; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004247:DNA; D017526:Receptor, IGF Type 1; D007930:Leucine