Targeting Neuropilin-1 to Inhibit VEGF Signaling in Cancer: Comparison of Therapeutic Approaches
Figure 3
VEGF Binding to VEGFR2 In Vivo Is Inhibited by Targeting Neuropilin-1
(A–C) The time course of VEGF–VEGFR2 complex formation on the endothelial cells following each of the three treatments. For blocking VEGF–Neuropilin-1 binding (B) and VEGFR–Neuropilin-1 coupling (C), this figure represents bolus intratissue protein delivery at time 0. For Neuropilin-1 expression blockade, insertion of Neuropilin-1 into the membrane decreases to the indicated level at time 0. The VEGF121–VEGFR2 binding curve is indistinguishable from the no-treatment line in each case. The tumor modeled here expresses 10,000 VEGFR2 and 100,000 Neuropilin per endothelial cell.
(D–F) Free (unbound) VEGF concentration in the interstitial space. *VEGF121 secreted at the same rate as VEGF165.
(G–I) The concentration of VEGF inhibitor in the interstitial space, or density of Neuropilin, on the blood vessel endothelial cell surface.