Effect of an insulin-like growth factor binding protein fusion protein on thymidine incorporation in neuroblastoma and rhabdomyosarcoma cell lines.
A fusion protein, FP 6/3, composed of IGF binding protein (IGFBP)-6 and IGFBP-3 was synthesized where the complete sequences of each binding protein were fused together into a single chimeric protein. The orientation of this fusion protein's structure has the N terminus of IGFBP-3 fused to the C terminus of IGFBP-6, leaving the key binding areas of each open. FP 6/3 bound to cells via its IGFBP-3 component and retained the increased affinity for IGF-II via its IGFBP-6 component. The effect of FP 6/3 on growth was determined in cell lines from both neuroblastoma and rhabdomyosarcoma, where IGF-II is an autocrine growth factor. In studies using FP 6/3, IGFBP-3, or IGFBP-6, a growth inhibition effect was shown for all when present under coincubation conditions with IGF-II. However, with transient exposure, FP 6/3 was the only IGFBP that retained this growth-inhibition property. Under transient exposure conditions, FP 6/3 was found to be effective when exposure was limited to as few as 10 min and concentrations were as low as 1 nm. These findings with FP 6/3 suggest that it potentially could lead be used as therapy against cancers in which IGF-II is an autocrine growth factor because it brings an inhibition action directly to tumor cells.
Dake
Brian L
BL
Department of Internal Medicine, The University of Iowa, Iowa City, Iowa 52246, USA.
Boes
Mary
M
Bach
Leon A
LA
Bar
Robert S
RS
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism / Q000494:pharmacology*; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000378:metabolism / Q000494:pharmacology*; D009447:Neuroblastoma; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D012208:Rhabdomyosarcoma; D013936:Thymidine / Q000493:pharmacokinetics
D018972:Insulin-Like Growth Factor Binding Protein 3; D018976:Insulin-Like Growth Factor Binding Protein 6; D011993:Recombinant Fusion Proteins; D013936:Thymidine