Insulin-Like Growth Factor-Binding Protein-1 and Prostate Cancer

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Abstract
There is growing and persuasive evidence, both experimental ( 1 - 4 ) and epidemiologic ( 5 - 7 ), that the peptide hormone insulin-like growth factor-I (IGF-I) is a critical factor in the development of prostate cancer. Because of their central role in the regulation of bioavailable IGF-I, the insulin-like growth factor-binding proteins (IGFBPs) have also come under scrutiny as potential mediators of prostate cancer risk ( 8 - 12 ). There is considerable disagreement concerning which, if any, of the IGFBPs are relevant to the development of prostate cancer. Epidemiologically, IGFBP-3 has been examined ( 5 , 7 ), primarily because more than 95% of circulating IGF-I is bound to this protein ( 13 ) together with an acid labile subunit (ALS, a protein synthesized in the liver). The IGF-I/IGFBP-3/ALS complex is too large (150 kd), however, to pass through blood vessel endothelial cells and affect target tissue ( 14 ). It is IGFBP-1 that effectively shuttles IGF-I across blood vessel membranes ( 15 , 16 ). Therefore, it would be expected that blood levels of IGFBP-1 be predictive of the amount of circulating IGF-I available to prostate tissue and thus of prostate cancer risk.

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