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 tumours secrete IGF-II in incompletely processed precursor forms. The ability of these pro-IGF-II forms to complex with the six IGF binding proteins (IGFBPs) is poorly understood. In this study, pro-IGF-II has been extracted from the serum and tumour tissue of two patients with non-islet cell tumour hypoglycaemia. These samples were used to study binary complex formation 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 form binary complexes with recombinant IGF-II or tumour-derived pro-IGF-II forms, when the preparations were standardised according to IGF-II immunoreactivity. As previously described, ternary complex formation by acid-labile subunit (ALS) with IGFBP-3 and pro-IGF-II was greatly decreased compared with complex formation with mature IGF-II. In contrast, ALS bound similarly to 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 complexes with IGFBP-3 as seen predominantly in normal serum. This may increase the tissue availability of serum pro-IGF-II, allowing its insulin-like potential to be realised.
Bond
J J
JJ
Cooperative Research Centre for Diagnostic Technologies, Brisbane, Queensland 4001, Australia.
Meka
S
S
Baxter
R C
RC
D000368:Aged; D000369:Aged, 80 and over; D001667:Binding, Competitive; D015153:Blotting, Western; D002352:Carrier Proteins; D005260:Female; D006023:Glycoproteins; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism*; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000378:metabolism
D002352:Carrier Proteins; D006023:Glycoproteins; D018970:Insulin-Like Growth Factor Binding Protein 1; 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; D018969:Insulin-Like Growth Factor Binding Proteins; D011498:Protein Precursors; D011994:Recombinant Proteins; C075944:insulin-like growth factor binding protein, acid labile subunit; C066038:proinsulin-like growth factor II; D007335:Insulin-Like Growth Factor II