Cell Surface Molecules Driving Breast Cancer/Endothelial Interactions
Abstract
Fibroblast growth factors (FGFs) are a family of 23 heparin-binding polypeptides with diverse biologic functions. FGF-2 is stored in an immobile, functionally inactive form in the extracellular matrix. Since FGF-2 exerts its biologic roles by binding to cell surface receptors, a major interest is how FGF-2 reaches the cell surface from its inactive pool in the extracellular matrix. While heparinases and proteases can cleave components of the extracellular matrix and thus release FGF-2, an alternative strategy is the secretion of a soluble binding protein, FGF-Binding Protein (FGF-BP) . Using a number of investigative techniques, our laboratory is studying the protein-protein interactions enabling this binding protein to function in its hypothesized role, that FGF-BP can release FGF-2 from its inactive reservoir in the extracellular matrix, making FGF-2 functionally available. We have produced two recombinant FGF-BP1 proteins, have documented reversible binding to FGF-2, and have extensively studied their protein-protein interactions. We have demonstrated that FGF-BP1 and heparansulfate compete for binding to FGF-2, and that FGF-2 can bind its receptor in the presence of FGF-BP1. We have also shown that, in numerous biologic systems, FGF-BP1 can positively modulate FGF-2 biologic activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA395469
Entities
People
- Ali Al-attar
Organizations
- Georgetown University