Autonomous growth of a human neuroblastoma cell line is mediated by insulin-like growth factor II.
Insulin-like growth factor II (IGF-II) mRNA was increased in two of eight neuroblastomas and in eight of eight pheochromocytomas, tumors of the adrenal medulla that occur in childhood and adulthood, respectively. RNA encoding the type I IGF receptor, the receptor thought to mediate the mitogenic effects of IGF-I and IGF-II, also was uniformly expressed in these cells. To assess the role of IGF-II in the growth of these tumor cells, we have used the SK-N-AS cultured neuroblastoma cell line, which can be continuously propagated in mitogen-free medium, as a model system. Our results strongly suggest that IGF-II, synthesized by SK-N-AS cells and acting through type I IGF receptors, contributes to the autonomous growth of this tumor cell line. (a) SK-N-AS cells synthesized large amounts of IGF-II RNA and secreted greater than 50 ng/ml of IGF-II (as determined by specific radioimmuno- and radioreceptor assays). Little, if any, IGF-I RNA or immunoreactive IGF-I were detected. (b) SK-N-AS cells possess type I IGF receptors. (c) Exogenous IGF-I and IGF-II stimulated DNA synthesis in SK-N-AS cells, and this stimulation was abolished by a blocking antibody to the type I IGF receptor. (d) This anti-receptor antibody also abolished the multiplication of SK-N-AS cells in the absence of added mitogens. We conclude that IGF-II is an autocrine growth factor for SK-N-AS cells and suggest that this mechanism may contribute to the growth of some adrenal medullary tumors.
El-Badry
O M
OM
Molecular Genetics Section, National Cancer Institute, Bethesda, Maryland 20892.
Romanus
J A
JA
Helman
L J
LJ
Cooper
M J
MJ
Rechler
M M
MM
Israel
M A
MA
D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000313:Adrenal Medulla / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000502:physiology; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D008934:Mitogens; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D010673:Pheochromocytoma / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000032:analysis / Q000276:immunology; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D000911:Antibodies, Monoclonal; D003470:Culture Media; D008934:Mitogens; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013936:Thymidine