Distribution of VEGF and its receptors for each tissue. The diseased compartment represents a 4-cm diameter tumor. Vascular permeability of healthy tissue, = 4 × 10-8 cm/s; vascular permeability of the tumor = 4 × 10-7 cm/s; VEGF plasma clearance c
= 0.0206 min-1 ; VEGFR1 = 10,000 and VEGFR2 = 10,000 molecules/endothelial cell; NRP1 = 10,000 molecules/endothelial cell in the healthy tissue; VEGF165 secretion rate in healthy tissue q
= 0.102 molecule/cell/s; tumor VEGF165 secretion rate q
= 0.076 or 0.025 molecule/cell/s for 10,000 (written in black) or 100,000 (written in dark yellow) NRP1 in tumor respectively. A, From center out, discs represent: total VEGF, VEGF121 and VEGF165 distributions. In the healthy tissue, about half of the total VEGF distribution is in the form of the ternary complex VEGF165 bound to VEGFR2 and NRP1, leaving 24% bound to the ECM. In the tumor, most total VEGF is bound to the ECM (68% and 41% for 10,000 and 100,000 NRP1 in tumor, respectively). Most of the remaining total VEGF population is in the form of the ternary complex VEGF165 bound to VEGFR2 and NRP1 (15% and 48% for 10,000 and 100,000 NRP1 in tumor, respectively). Most of VEGF121 isoform is bound to VEGFR1 and NRP1 simultaneously. The vast majority of the free VEGF distribution in the blood is in the isoform VEGF165 (91%). B, Receptor occupancy. From center out, discs represent: overall receptor, NRP1, VEGFR2, VEGFR1 occupancies. The initial receptor densities dictate the receptor occupancies. For identical NRP1 receptor densities (10,000), the healthy tissue and the tumor have the same receptor occupancies: 60% of all the receptors are in their free states and 33% are in the complex form VEGFR1-NRP1. If the NRP1 density is increased by 10-fold in the tumor, most of the total receptors are free NRP1 (81%) and a small fraction is bound to VEGFR1 (9%).