Schematic summary of cell-based simulations of tumor angiogenesis (see [65, 66]). Tumor cells secrete VEGF that stimulates EC, and the model distinguishes between tip and stalk EC phenotypes. The tip cells respond by moving chemotactically towards higher concentrations of VEGF using the matrix fibers for support. They are also capable of degrading the ECM. VEGF-stimulated stalk cells can proliferate and/or move behind a tip cell. Thus, vessels emerge that follow the chemotactic path of the endothelial tip cells. As anastomoses occur, a network of vessels is formed. In the model by Mahoney et al. [66], oxygen is also secreted from the endothelial cells that belong to closed loops. It diffuses through the medium and reaches the tumor, where it is consumed by the tumor cells. Cellular dynamics (grey boxes and solid line arrows) are modeled by using CPM, the VEGF, and O2 profiles by continuous models based on the diffusion equation (white boxes and dashed line arrows).
