Insulin-like growth factor-binding protein 6 (IGFBP6) is a 24-kDa protein that binds insulin-like growth factor 1 (IGF-1) and IGF-2 with high affinity and inhibits IGF action in vitro. The Insulin-like growth factor-binding protein also known as IGFBP serves as a carrier protein for Insulin-like growth factor 1. IGFBPs are distinct but are sharing regions with strong homology. All members of the IGFBP family bind IGF-I and IGF-II with about equal affinity. Insulin-like growth factor (IGF) binding proteins (IGFBPs) have been shown to either inhibit or enhance the action of IGF or act in an IGF-independent manner in the prostate. IGF-binding protein-4 (IGFBP-4) inhibits IGF-I action in vitro and is the most abundant IGFBP in the rodent arterial wall. IGFBP6 is directly downregulated by the beta-catenin/TCF complex in desmoid tumors, and imply a role for the IGF axis in the proliferation of desmoid tumors. There is mounting evidence that the structure of the IGFBP proteins plays a key role in the regulation of IGF bioavailability, by modulating its molecular size, capillary membrane permeability, target tissue specificity, cell membrane adherence, and IGF affinity.
Insulin-like growth factor-binding protein 7(IGFBP-7) is a secreted glycosylated protein that contains three protein domain modules. IGFBP7 contains an N-terminal IGFBP domain, followed by a Kazal-type serine proteinase inhibitor domain and a C-terminal immunoglobulin-like C2-type domain. Human and mouse IGFBP7 are highly homologous and share 94% aa sequence identity. It is expressed in many normal tissues and in cancer cells. It is abundantly expressed in high endothelial venules (HEVs) of blood vessels in the secondary lymphoid tissues. It binds IGF and insulin with very low affinity and has been shown to enhance the mitogenic actions of IGF and insulin. IGFBP7 also has IGF/insulin-independent activities. It interacts with heparan sulfate proteoglycans, type IV collagen, and specific chemokines. It supports weak cell adhesion, promotes cell spreading on type IV collagen, and stimulates the production of the potent vasodilator PGI2. It modulates tumor cell growth and has also been implicated in angiogenesis.
Insulin-Like Growth Factor II (IGF2) belongs to the insulin family of polypeptide growth factors that is involved in development and growth. Members of this family are structurally homologous to proinsulin, and share higher sequence identity. IGF2 is expressed only from the paternally inherited allele and believed to be secreted by the liver and to circulate in the blood. IGF2 possess growth-promoting activity and can stimulate the proliferation and survival of various cell types including muscle, bone, and cartilage tissue in vitro. IGF2 is influenced by placental lactogen and may play a role in fetal development.
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