Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice

Cancer Cell. 2003 Jul;4(1):31-9. doi: 10.1016/s1535-6108(03)00168-5.


Tumor vasculature is hyperpermeable to macromolecules compared to normal vasculature; however, the relationship between tumor hyperpermeability and tumor progression is poorly understood. Here we show that a cell-permeable peptide derived from caveolin-1, termed cavtratin, reduces microvascular hyperpermeability and delays tumor progression in mice. These antipermeability and antitumor actions of cavtratin occur in the absence of direct cytostatic or antiangiogenic effects. Cavtratin blocks microvascular permeability by inhibiting endothelial nitric oxide synthase (eNOS), as the antipermeability and antitumor actions of cavtratin are markedly diminished in eNOS knockout mice. Our results support the concepts that hyperpermeability of tumor blood vessels contributes to tumor progression and that blockade of eNOS may be exploited as a novel target for antitumor therapy.

Publication types

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

MeSH terms

  • Animals
  • Capillary Permeability*
  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / prevention & control*
  • Carcinoma, Lewis Lung / blood supply
  • Carcinoma, Lewis Lung / pathology
  • Carcinoma, Lewis Lung / prevention & control*
  • Caveolin 1
  • Caveolins / therapeutic use*
  • Disease Progression
  • Endothelium, Vascular / cytology
  • Enzyme Inhibitors / pharmacology
  • Liver Neoplasms, Experimental / blood supply
  • Liver Neoplasms, Experimental / pathology
  • Liver Neoplasms, Experimental / prevention & control
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Neovascularization, Physiologic / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Peptide Fragments / therapeutic use*
  • Vascular Endothelial Growth Factor A / physiology


  • Cav1 protein, mouse
  • Caveolin 1
  • Caveolins
  • Enzyme Inhibitors
  • Peptide Fragments
  • Vascular Endothelial Growth Factor A
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse