title: Unraveling insulin-like growth factor binding protein-3 actions in human disease.
abstract: The 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.
authors.affiliation: Department of Pathology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298-0662, USA.
authors.forename: Sherryline
authors.initials: S
authors.lastname: Jogie-Brahim
authors.forename: David
authors.initials: D
authors.lastname: Feldman
authors.forename: Youngman
authors.initials: Y
authors.lastname: Oh
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D017124:Conserved Sequence; D015870:Gene Expression; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000453:epidemiology*; D011110:Polymorphism, Genetic; D011485:Protein Binding; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011956:Receptors, Cell Surface; D012307:Risk Factors; D013002:Somatomedins / Q000378:metabolism*
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D011956:Receptors, Cell Surface; D013002:Somatomedins; D017526:Receptor, IGF Type 1