Molecular polarity in endothelial cells and tumor-induced angiogenesis

Oncol Res. 2000;12(1):1-4. doi: 10.3727/000000001108747372.


Endothelial cells expose receptors for vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) at the abluminal, basal surface that work as basic regulators of tumor-induced angiogenesis. Their specific localization makes them susceptible to the activity of tumor-released stimulatory factors, like VEGF/VPF, which induce proliferation of the endothelial cell toward the extracellular matrix. At the same time, VEGF/VPF stimulates endothelial cells to expose tissue factor (TF), the high-affinity transmembrane receptor and cofactor for cellular initiation of the plasma coagulation protease cascades through the extrinsic pathway, so generating thrombin. Thrombin exerts a number of activities: it forms an extracellular fibrin barrier from the VEGF/VPF-dependent fibrinogen extravasation; it activates progelatinase-A (pro-MMP-2), which destroys the basal membrane, allowing proliferation of endothelial cells (ECs) in the novel tumoral fibrin matrix; finally, it induces EC proliferation, potentiating the VEGF effect. Another important factor exposed at the abluminal endothelial cell surface is membrane type 1 matrix metalloproteinase (MT1-MMP), a membrane-bound metalloproteinase, which also activates progelatinase-A, allowing an alternative pathway to that of thrombin to destroy the basal membrane. In addition, we will see that MT1-MMP is also engaged in a direct, cell-associated fibrinolytic activity, essential for tubulogenesis of the novel outsprouting capillary.

Publication types

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

MeSH terms

  • Blood-Brain Barrier / physiology
  • Cell Polarity / physiology*
  • Endothelial Growth Factors / physiology
  • Endothelium, Vascular / metabolism*
  • Enzyme Precursors / metabolism
  • Fibrin / metabolism
  • Fibrinolysis / physiology*
  • Gelatinases / metabolism
  • Humans
  • Lymphokines / physiology
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / metabolism
  • Neovascularization, Pathologic / chemically induced
  • Neovascularization, Pathologic / metabolism*
  • Thrombin / metabolism
  • Thromboplastin / metabolism
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Enzyme Precursors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Fibrin
  • Thromboplastin
  • Thrombin
  • Gelatinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • progelatinase