Heparin potentiates Avastin-mediated inhibition of VEGF binding to fibronectin and rescues Avastin activity at acidic pH [Cell Biology]

In this study, we investigated Avastin's capacity to modulate VEGF165 binding to porcine aortic endothelial cells and to heparin and fibronectin (FN) across a range of pH values (pH 5–8). We observed that Avastin slightly enhanced VEGF binding to heparin and that heparin increased VEGF binding to Avastin. In contrast, Avastin inhibited VEGF binding to cells and FN, yet Avastin could still bind to VEGF that was bound to FN, indicating that these binding events are not mutually exclusive. Avastin binding to VEGF was dramatically reduced at acidic pH values (pH 5.0–6.5), whereas VEGF binding to FN and nonreceptor sites on cells was enhanced. Interestingly, the reduced Avastin–VEGF binding at acidic pH was rescued by heparin, as was Avastin's ability to inhibit VEGF binding to cells. These results suggest that heparin might be used to expand the clinical utility of Avastin. Our findings highlight the importance of defining the range of VEGF interactions to fully predict antibody activity within a complex biological setting.

Source: Journal of Biological Chemistry - November 14, 2019 Category: Chemistry Authors: Divyabharathy Tsiros, Casey E. Sheehy, Surenna Pecchia, Matthew A. Nugent Tags: Glycobiology and Extracellular Matrices Source Type: research