IGFBPs and cancer.

The proposed insulin-like growth factor binding protein (IGFBP) superfamily are a group of secreted proteins that are structurally, functionally and evolutionarily related, and include six IGFBPs and over 10 IGFBP-related proteins. The IGFBPs have high affinities for insulin-like growth factors (IGFs), thereby modulating the mitogenic, anti-apoptotic and metabolic actions of IGFs. In addition, IGFBPs, particularly IGFBP-3, also have IGF-independent, anti-proliferative and pro-apoptotic functions. The IGFBPs are, in turn, modulated by proteolysis. Epidemiological data correlating serum IGF/IGFBP levels with the risk of several human cancers suggest a possible protective role for IGFBP-3. In vitro studies suggest that the potential protective effects of IGFBP-3 involve both IGF-dependent and IGF-independent mechanisms. Further studies are necessary to demonstrate whether the ability of IGFBPs to inhibit the proliferation of cancer cells under in vitro conditions has significant clinical implications.