Effect of an Insulin-Like Growth Factor Binding Protein Fusion Protein on Thymidine Incorporation in Neuroblastoma and Rhabdomyosarcoma Cell Lines

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Abstract

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.

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