Binding characteristics of pro-insulin-like growth factor-II from cancer patients: binary and ternary complex formation with IGF binding proteins-1 to -6

Many rumours secrete IGF-II in incompletely processed precursor forms. The ability of these pro-IGF-II forms to complex with the six IGF binding prote ins (IGFBPs) is poorly understood. In this study, pro-IGF-II has been extra cted from the serum and tumour tissue of two patients with non-islet cell t umour hypoglycaemia. These samples were used to study binary complex format ion with IGFBPs-1 to -6 using competitive IGF-II binding assays and ternary complex formation with IGFBP-3 and IGFBP-5. In each case, IGFBPs-1 to -6 showed little difference in their ability to f orm binary complexes with recombinant IGF-II or tumour-derived pro-IGF-II f orms, when the preparations were standardised according to IGF-II immunorea ctivity. As previously described, ternary complex formation by acid-labile subunit (ALS) with IGFBP-3 and pro-IGF-II was greatly decreased compared wi th complex formation with mature IGF-II. In contrast, ALS bound similarly t o IGFBP-5 in the presence of pro-IGF-II and mature IGF-II. These studies suggest that pro-IGF-II preferentially forms binary complexes with IGFBPs, and ternary complexes with IGFBP-5, rather than ternary compl exes with IGFBP-3 as seen predominantly in normal serum. This may increase the tissue availability of serum pro-IGF-II, allowing its insulin-like pote ntial to be realised.