Novel aspects of the insulin-like growth factor binding proteins

The insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and IGFBP proteases regulate somatic growth and cellular proliferation both in vivo and in vitro. IGFs are potent mitogens whose actions are determined by the availability of free IGFs to interact with IGF receptors. IGFBPs comprise a family of six proteins that bind IGFs with high affinity and specificity and thereby regulate IGF-dependent actions. IGFBPs have also recently emerged as IGF-independent regulators of cell growth. Several IGFBP association proteins have been discovered recently which can affect IGFBP action. Cleavage of IGFBPs by specific proteases modulates levels of free IGFs and IGFBPs and thereby their actions. IGFBP-related proteins (IGFBP-rPs) are an emerging group of proteins which bind IGFs with low affinity and also play important roles in cell growth and differentiation. The IGFBPs appear to have emerging roles in the mechanisms underlying human cancer. The GH-IGF-IGFBP axis is complex and powerful. Future research on its physiology promises exciting insights into cell biology as well as advancements in the treatment of a wide range of disease states including cancer, diabetes, vascular disease, asthma, and growth disorders.