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lüll Biology of insulin-like growth factor binding protein-4 and its role in cancer (review) Durai R; Davies M; Yang W; Yang SY; Seifalian A; Goldspink G; Winslet MInt J Oncol 2006[Jun]; 28 (6): 1317-25Insulin-like growth factor binding protein-4 (IGFBP-4) is an important member of the insulin-like growth factor (IGF) system. The IGFBP-4 has three domains of which the N-terminal sequence is important for the binding of IGF. It acts as a transport protein for IGF-I and IGF-II and modulates their biological effects. There is increasing evidence that IGFBP-4 inhibits IGF-induced cellular growth both in vitro and in vivo. IGFBP-4 can also mediate its actions through a mechanism independent of IGFs. IGFBP-4 level and expression in various tissues are influenced by IGFBP protease, nutrition, several growth factors and hormones. Overexpression of IGFBP-4 in transgenic animal models causes reduced growth of organs containing smooth muscle. Most cancers express IGFBP-4 at levels which correlate with their state of differentiation. However, the effects of IGFBP-4 on tumor growth are uncertain. In vitro studies have shown that overexpression of IGFBP-4 inhibit the growth of some colon cancer cells. Overexpression of IGFBP-4 in vivo has been reported to decrease the growth of prostate cancer. The effect of altered expression of IGFBP-4 in vivo in colon and other cancers needs to be explored as locally available IGFs appear to stimulate mitogenesis.|Animals[MESH]|Cell Division/drug effects/physiology[MESH]|Cell Line, Tumor[MESH]|Disease Models, Animal[MESH]|Humans[MESH]|Insulin-Like Growth Factor Binding Protein 4/genetics/pharmacology/*physiology[MESH]|Male[MESH]|Neoplasms/*pathology[MESH]|Prostatic Neoplasms/pathology[MESH] |