Insulin-Like Growth Factor Binding Protein-1 Interacts With Integrins to Inhibit Insulin-Like Growth Factor-Induced Breast Cancer

Abstract : The insulin-like growth (IGF) system and extracellular matrix proteins are key regulators of the malignant breast cancer phenotype. Both IGFs and extracellular matrix proteins communicate with epithelial cells by ligating cell surface receptors. Therefore ligand-receptor interactions of the two systems are relevant treatment targets in breast cancer. Studies have shown that IGFBP-1 can bind to IGF and prevent GE from interacting with its receptor and inhibit breast cancer cell growth. IGFBP-1 has also been shown to interact with extracellular matrix protein receptors, integrins, on the cell surface through an Arg-Gly-Asp (RGD) integrin recognition sequence. This work-in-progress will test the hypothesis that IGFBP-I interrupts ligand-receptor interactions between extracellular matrix proteins and integrins. The key research accomplishment is the cloning and expression of a mutant IGFBP-1 protein species that will not interact with integrins. The successful expression and purification of the mutant IGFBP-1 protein is needed to test whether IGFBP-1 can be used as a strategy to neutralize integrin function in an RGD-dependent mechanism. The long-term goal is to provide evidence that IGFBP-1 is a novel therapy for the treatment of breast cancer.