Targeting Neuropilin-1 to Inhibit VEGF Signaling in Cancer: Comparison of Therapeutic Approaches
Figure 2
Interactions between VEGF121, VEGF165, and Their Cell Surface Receptors VEGFR1, VEGFR2, and Neuropilin-1, and Interstitial GAG Binding Sites
(A) VEGF121 binds to VEGFR2 but not Neuropilin-1. VEGF165 binds both receptors as well as GAG chains in the interstitial space. VEGF165 bound to Neuropilin-1 can diffuse laterally on the cell membrane and bind VEGFR2 (and vice versa), coupling these receptors together, even though the receptors themselves do not interact.
(B) VEGF121 and VEGF165 both bind VEGFR1. Neuropilin-1 and VEGFR1 interact directly, forming a complex that is permissive for VEGF121 binding but not VEGF165.
(C) Inhibition of Neuropilin-1 expression results in a decrease in the insertion rate of Neuropilin receptors into the cell membrane (sN).
(D) PlGF2Δ, a fragment of placental growth factor, competes with VEGF165 for the binding site on Neuropilin-1.
(E) An antibody to Neuropilin-1 that does not interfere with VEGF165 binding can block the coupling of VEGF165–Neuropilin to VEGFR2, resulting in sequestration of VEGF on nonsignaling Neuropilin.