Mitogenic and antiapoptotic effects of insulin-like growth factor binding protein-6 in the human osteoblastic osteosarcoma cell line Saos-2/B-10.
Insulin-like growth factor (IGF) I is a potent mitogen for human osteosarcoma cells such as the Saos-2/B-10 cell line. IGF binding proteins (IGFBPs) prevent stimulation of DNA synthesis by IGFs. In contrast to recombinant human (rh) IGFBP-2, -3, -4, and -5, 10-100 nM rhIGFBP-6 stimulated [(3)H]thymidine incorporation into DNA and multiplication of Saos-2/B-10 cells. Upon withdrawal of serum, 30 nM IGFBP-6 also decreased apoptosis (within 4 h) and increased protein content and sodium-dependent phosphate uptake (within 24 h), but less potently than IGF I. (125)I-labeled rhIGFBP-6 did not bind to the cells, and cold IGFBP-6 did not affect (125)I-labeled IGF I binding. Production of IGF I, IGF II, and IGFBP-6 by the cells or significant degradation of rhIGFBP-6 could not be detected within 24 h of incubation. Thus, among the rhIGFBPs tested, rhIGFBP-6 is unique in stimulating osteosarcoma cell growth. Furthermore, it has an antiapoptotic effect.
Schmid
C
C
Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, Rämistrasse 100, Zürich, CH-8091, Switzerland.
Keller
C
C
Gosteli-Peter
M
M
Zapf
J
J
D000469:Alkaline Phosphatase / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms; D002455:Cell Division / Q000187:drug effects*; D016895:Culture Media, Serum-Free; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000494:pharmacology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000494:pharmacology; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000494:pharmacology; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000494:pharmacology; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000494:pharmacology* / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009707:Nucleosomes / Q000187:drug effects / Q000502:physiology; D012516:Osteosarcoma; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D018976:Insulin-Like Growth Factor Binding Protein 6; D009707:Nucleosomes; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D000469:Alkaline Phosphatase