The receptor tyrosine kinase inhibitor SU11248 impedes endothelial cell migration, tubule formation, and blood vessel formation in vivo, but has little effect on existing tumor vessels

Angiogenesis. 2004;7(3):225-33. doi: 10.1007/s10456-004-3149-y.


Antiangiogenic agents produce regression in few tumors in clinical trials, but are effective in preventing recurrences. To determine whether the vascular endothelial growth factor (VEGF) receptor is a molecular target to prevent metastatic disease, we utilized a non-specific inhibitor of the VEGF receptor, SU11248. This receptor tyrosine kinase (RTK) inhibitor prevented migration of endothelial cells and markedly attenuated capillary-like tubule formation in endothelial cells in culture. Similarly, this agent prevented blood vessel formation in the tumor vascular window model. VEGF RTK inhibition produced minimal effects on established blood vessels in the tumor vascular window model and little effect on blood flow studied by power Doppler analysis. To determine whether these agents attenuate the development of metastases, Lewis lung carcinoma tumors were resected from the dorsal skin and lung metastases were quantified with and without treatment with SU11248. The RTK inhibitor attenuated the formation of lung metastases following resection of the hind limb tumor. In contrast, these agents did not induce regression of primaries but slowed the progression of tumor growth. These findings suggest that the greatest role for VEGF antagonists may be to prevent the formation of new blood vessels, during and after conventional therapy is given to existing neoplastic disease.

Publication types

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

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Apoptosis
  • Blood Vessels / drug effects
  • Carcinoma, Lewis Lung / blood supply*
  • Carcinoma, Lewis Lung / drug therapy
  • Cell Movement / drug effects
  • Cells, Cultured
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology
  • Humans
  • Indoles / pharmacology*
  • Indoles / therapeutic use
  • Intracellular Signaling Peptides and Proteins / pharmacology*
  • Intracellular Signaling Peptides and Proteins / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Metastasis / prevention & control
  • Neovascularization, Pathologic / drug therapy
  • Pyrroles / pharmacology*
  • Pyrroles / therapeutic use
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Secondary Prevention
  • Sunitinib
  • Umbilical Cord / cytology


  • Angiogenesis Inhibitors
  • Indoles
  • Intracellular Signaling Peptides and Proteins
  • Pyrroles
  • protein kinase modulator
  • Receptors, Vascular Endothelial Growth Factor
  • Sunitinib