Effects of endothelial cell proliferation and migration rates in a computational model of sprouting angiogenesis

Sci Rep. 2016 Nov 14:6:36992. doi: 10.1038/srep36992.

Abstract

Angiogenesis, the recruitment of new blood vessels, is a critical process for the growth, expansion, and metastatic dissemination of developing tumors. Three types of cells make up the new vasculature: tip cells, which migrate in response to gradients of vascular endothelial growth factor (VEGF), stalk cells, which proliferate and extend the vessels, and phalanx cells, which are quiescent and support the sprout. In this study we examine the contribution of tip cell migration rate and stalk cell proliferation rate on the formation of new vasculature. We calculate several vascular metrics, such as the number of vascular bifurcations per unit volume, vascular segment length per unit volume, and vascular tortuosity. These measurements predict that proliferation rate has a greater effect on the spread and extent of vascular growth compared to migration rate. Together, these findings provide strong implications for designing anti-angiogenic therapies that may differentially target endothelial cell proliferation and migration. Computational models can be used to predict optimal anti-angiogenic therapies in combination with other therapeutics to improve outcome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement
  • Cell Proliferation
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Models, Theoretical*
  • Neovascularization, Physiologic*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Vascular Endothelial Growth Factor A