Evidence for the Involvement of Endothelial Cell Integrin alphaVbeta3 in the Disruption of the Tumor Vasculature Induced by TNF and IFN-gamma

Nat Med. 1998 Apr;4(4):408-14. doi: 10.1038/nm0498-408.

Abstract

Administration of tumor necrosis factor (TNF) and gamma interferon (IFN-gamma) to melanoma patients causes selective disruption of the tumor vasculature but the mechanism of this disruption is unknown. Here we report that exposure of human endothelial cells to TNF and IFN-gamma results in a reduced activation of integrin alphaVbeta3, an adhesion receptor that plays a key role in tumor angiogenesis, leading to a decreased alphaVbeta3-dependent endothelial cell adhesion and survival. Detachment and apoptosis of angiogenic endothelial cells was demonstrated in vivo in melanoma metastases of patients treated with TNF and IFN-gamma. These results implicate integrin alphaVbeta3 in the anti-vascular activity of TNF and IFN-gamma and demonstrate a new mechanism by which cytokines control cell adhesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Biopsy
  • Cell Adhesion / drug effects
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology
  • Humans
  • Interferon-gamma / pharmacology*
  • Interferon-gamma / therapeutic use
  • Melanoma / blood supply*
  • Melanoma / pathology
  • Melanoma / therapy
  • Neoplasm Metastasis
  • Neovascularization, Pathologic / psychology
  • Receptors, Vitronectin / drug effects
  • Receptors, Vitronectin / physiology*
  • Recombinant Proteins / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Tumor Necrosis Factor-alpha / therapeutic use
  • Umbilical Veins

Substances

  • Receptors, Vitronectin
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma