Cell Surface Molecules Driving Breast Cancer/Endothelial Interactions
Abstract
Fibroblast Growth Factor-2 (FGF-2) is a biologic cytokine with a major role in tumorigenesis and angiogenesis, as well as in organogenesis and neuroprotection. FGF-Binding Protein 1 (BP1) has been suggested to bind, protect, and present FGF-2 to its receptor on the cell surface. Studies of this protein thus far have mainly relied on transfection or ribozyme- targeting protocols to evaluate its functional activity. We produced and purified two recombinant BP1 proteins, in prokaryotic and eukaryotic systems. We use recombinant BP1 to study the binding characteristics and functional activity of BP1. We show that recombinant BP1 can reversibly bind radiolabeled FGF-2, and that this binding can be inhibited by high doses of FGF-1, heparin, heparan sulfate, and pentosan polysulfate (PPS), a heparinoid presently in clinical trials. We demonstrate that recombinant BP1 can positively modulate FGF-2 activity in models of anchorage-independent growth and angio- genesis. We have used peptide phage display technology to investigate peptide sequences which may offer superior binding characteristics to FGF-2 or BP1. We are presently investigating the ability of BP1 to affect the role of FGF-2 in neuroprotection models. Additionally, we are investigating the intracellular signaling cascade of BP1-modulated FGF-2 activity. We conclude that BP1 reversibly binds and positively modulates the functional activity of FGF-2 in multiple models of FGF-2 mediated events.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA385305
Entities
People
- Ali Al-attar
Organizations
- Georgetown University