A cell-based model exhibiting branching and anastomosis during tumor-induced angiogenesis.
This work describes the first cell-based model of tumor-induced angiogenesis. At the extracellular level, the model describes diffusion, uptake, and decay of tumor-secreted pro-angiogenic factor. At the cellular level, the model uses the cellular Potts model based on system-energy reduction to describe endothelial cell migration, growth, division, cellular adhesion, and the evolving structure of the stroma. Numerical simulations show: 1), different tumor-secreted pro-angiogenic factor gradient profiles dramatically affect capillary sprout morphology; 2), average sprout extension speeds depend on the proximity of the proliferating region to the sprout tip, and the coordination of cellular functions; and 3), inhomogeneities in the extravascular tissue lead to sprout branching and anastomosis, phenomena that emerge without any prescribed rules. This model provides a quantitative framework to test hypotheses on the biochemical and biomechanical mechanisms that control tumor-induced angiogenesis.
Bauer
Amy L
AL
Department of Mathematics, University of Michigan, Ann Arbor, Michigan, USA.
Jackson
Trachette L
TL
Jiang
Yi
Y
D043924:Angiogenesis Modulating Agents; D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D002449:Cell Aggregation; D002450:Cell Communication; D049109:Cell Proliferation; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000503:physiopathology*
D043924:Angiogenesis Modulating Agents; D042501:Angiogenic Proteins