Background |
Insulin-like growth factor (IGF) signaling plays a major role in regulating the proliferation and metabolism of normal and malignant cells. Insulin-like growth factor-binding proteins (IGFBPs) play an integral role in modifying IGF actions in a wide variety of cell types. The six IGFBP family members share a high affinity for IGF binding and are structurally related, but are encoded by distinct genes. IGF binding proteins can exert stimulatory or inhibitory effects by controlling IGF availability through high affinity binding of IGF at the carboxy-terminal domain. IGFBP3 is the most abundant serum IGF binding protein and the main mediator for IGF-I bioactivities. IGFBP3 also binds IGF-II, insulin, and other cellular and extracellular components to regulate cell growth, development, and apoptosis through both IGF-dependent and IGF-independent mechanisms. Research studies describe correlations between increased IGF-I levels and reduced levels of IGFBP3 with increased risks of developing cancer, including breast, colon, lung, and prostate cancer. |