Whole-body changes in response to VEGF secretion by a tumor. The diseased compartment represents a 4-cm diameter tumor. Vascular permeability of the healthy tissue, = 4 × 10-8 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 (black lines) or 100,000 (dark yellow lines) NRP1 in tumor respectively. The normal tissue VEGF level is insensitive to the variation of each of the parameters considered here. A, The free VEGF concentration in the tumor and in the blood are approximately linearly dependent on tumor VEGF secretion rate. The tumor VEGF level decreases while the blood VEGF level increases when increasing the vascular permeability in tumor from = 4 × 10-7 cm/s (dotted lines) to 4 × 10-5 cm/s (dashed lines). B, Increasing vascular permeability in tumor decreases free VEGF in the tumor and slightly increases blood VEGF. Increasing the NRP1 receptor density increases the VEGF level in tumor for vascular permeability in tumor higher than 4 × 10-7 cm/s. C, Decreasing the clearance rate of VEGF increases free VEGF in the blood and tumor. Increasing the density of NRP1 receptors in the tumor has an effect only for higher permeability = 4 × 10-5 cm/s, drastically lowering free VEGF concentration in the tumor. D, Increasing vascular permeability in the healthy tissue results in increased free VEGF in the blood and tumor by several-fold. Vascular permeability in the tumor = 4 × 10-7 cm/s.