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lüll Unraveling insulin-like growth factor binding protein-3 actions in human disease Jogie-Brahim S; Feldman D; Oh YEndocr Rev 2009[Aug]; 30 (5): 417-37The IGF system plays critical roles in somatic growth in an endocrine fashion (somatomedin hypothesis) as well as proliferation and differentiation of normal and malignant cells in a paracrine/autocrine fashion. IGFBP-3 is known to modulate the actions of IGFs in circulation as well as the immediate extracellular environment. Interestingly, apart from the ability to inhibit or enhance IGF actions, IGFBP-3 also exhibits very clear, distinct biological effects independent of the IGF/IGF-I receptor axis. Over the past decade it has become widely appreciated that IGF/IGF-IR-independent actions of IGFBP-3 (antiproliferative and proapoptotic effects) contribute to improving the pathophysiology of a variety of human diseases, such as cancer, diabetes, and malnutrition. Recent studies have implicated interaction of IGFBP-3 with a variety of proteins or signaling cascades critical to cell cycle control and apoptosis; however, the actual mechanism of IGFBP-3 action is still unclear. This review reinforces the concept in support of the IGF/IGF-IR axis-independent actions of IGFBP-3 and delineates potential underlying mechanisms involved and subsequent biological significance, focusing in particular on functional binding partners and the clinical significance of IGFBP-3 in the assessment of cancer risk.|Active Transport, Cell Nucleus[MESH]|Animals[MESH]|Cell Differentiation[MESH]|Cell Nucleus/metabolism[MESH]|Cell Proliferation[MESH]|Conserved Sequence[MESH]|Gene Expression[MESH]|Humans[MESH]|Insulin-Like Growth Factor Binding Protein 3[MESH]|Insulin-Like Growth Factor Binding Proteins/chemistry/genetics/*physiology[MESH]|Neoplasms/*epidemiology[MESH]|Polymorphism, Genetic[MESH]|Protein Binding[MESH]|Receptor, IGF Type 1/metabolism[MESH]|Receptors, Cell Surface[MESH]|Risk Factors[MESH]|Somatomedins/*metabolism[MESH] |