EPC contribution to tumor angiogenesis.(A) The angiogenic activity α as a function of position for tumors of different radii: R_t ≈ 0.5 mm, t ≈ 10 days (d); R_t ≈ 1.0 mm, t ≈ 20 d; and R_t ≈ 1.5 mm, t ≈ 25 d. As the tumor grows, the highest angiogenic activity becomes localized near the periphery and extends beyond the tumor boundary for a distance approximately equal to the tumor radius, meaning that angiogenesis is stimulated in the adjacent normal tissue as well. Far from the tumor, α approaches zero, indicating a balance between angiogenesis stimulators and inhibitors resulting in a stable vascular network. The inset shows the correlation between experimental perfusion measurements¹⁰  and angiogenic activity. (B) Total vascular density as a function of position for tumors of different radii. The tumor initially has a radius of 300 μm and a vascular density equal to that of the normal tissue. Since the vascular density profiles are assumed to mirror the α profiles⁹  (A), the highest vascular density becomes localized near the periphery as the tumor grows. Vascular volume also increases with tumor size as expected (inset). (C) Model predictions of total vascular density agree well with experimental data¹⁷  during the early stages of tumor growth. Experimental data are given as means ± SD. (D) EPC-derived vascular density as a function of position for tumors of different radii. EPC proliferation makes only a modest contribution to vascular density compared with the case in which EPCs do not proliferate. The inset shows the predicted increase in EPC-derived vascular volume fraction as tumor size increases.