Insulin-like growth factors (IGFs)-I and -II are small secreted peptides that stimulate the survival, and promote the proliferation and differentiation, of many cell types []. In biological fluids, these growth factors are usually bound to IGF binding proteins (IGFBPs), which regulate their availability and activity by prolonging their half-life and modulating their receptor interactions. To date, six IGFBP family members have been identified (termed IGFBP1-6) []. They share a conserved gene (intron-exon) organisation and high IGF binding affinity. Structurally, the proteins also share a common domain architecture, possessing a conserved N-terminal IGFBP domain, a highly variable mid-section, and a thyroglobulin type-1 (Tg1) domain in their C-terminal regions. In addition to their role in the regulation of IGF activity, there is evidence for the direct association of IGFBPs with a variety of extracellular and cell surface molecules [, ], with consequent effects upon important biological processes. These include modulation of bone cell proliferation [], and growth arrest of breast and prostate cancer cells [, ]. IGFBP4 is abundant in serum, and is expressed in many different tissues. The protein functions as a cardiogenic growth factor in mice -an effect that is IGF-independent, and mediated by inhibition on the canonical Wnt signalling pathway [].
