A cell-based model exhibiting branching and anastomosis during tumor-induced angiogenesis

Biophys J. 2007 May 1;92(9):3105-21. doi: 10.1529/biophysj.106.101501. Epub 2007 Feb 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Angiogenesis Modulating Agents
  • Angiogenic Proteins / metabolism*
  • Animals
  • Cell Aggregation
  • Cell Communication*
  • Cell Proliferation
  • Computer Simulation
  • Humans
  • Models, Biological*
  • Neoplasms / blood supply*
  • Neoplasms / pathology
  • Neoplasms / physiopathology*
  • Neovascularization, Pathologic / pathology*
  • Neovascularization, Pathologic / physiopathology*

Substances

  • Angiogenesis Modulating Agents
  • Angiogenic Proteins