Targeting Neuropilin-1 to Inhibit VEGF Signaling in Cancer: Comparison of Therapeutic Approaches
Figure 7
Tissue Specificity of Neuropilin-Targeted Inhibition of VEGF Signaling
Tissues that express low levels of Neuropilin-1 are insensitive to all Neuropilin-targeting treatments. The inhibition of VEGF–VEGFR2 signaling is directly proportional to Neuropilin-1 density (A–C), except at very high Neuropilin levels, which can overcome the inhibition. Tissues that express intermediate and high levels of Neuropilin-1 are further distinguished by the level of expression of VEGFR1. Blocking VEGFR–Neuropilin coupling is the most effective treatment to reduce VEGF–VEGFR2 signaling for tissues with any VEGFR1 expression level. However, in high VEGFR1 tissues, the other treatments are also quite effective. All three treatments significantly induce VEGF–VEGFR1 complex formation (D–F). The circles in each figure denote the conditions for Figures 3 and 4 (left, VEGFR1 actually zero in simulations) and Figures 5 and 6 (right) to compare the efficacy of the treatments for different tumors. The results shown are for a Neuropilin-1 expression knockdown to 1%, for 1 μM PlGF2Δ, and 1 μM AbNRP.