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Evidence for the involvement of endotheliai cell integrin αVβ3 in the disruption of the tumor vascuiature induced by TNF and IFN-γ

Nature Medicinevolume 4pages408414 (1998) | Download Citation

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Abstract

Administration of tumor necrosis factor (TNF) and γ interferon (IFN-γ) to melanoma patients causes selective disruption of the tumor vascuiature but the mechanism of this disruption is unknown. Here we report that exposure of human endotheliai cells to TNF and IFN-γ results in a reduced activation of integrin αVβ3, an adhesion receptor that plays a key role in tumor angiogenesis, leading to a decreased αVβ3-dependent endotheliai cell adhesion and survival. Detachment and apoptosis of angiogenic endotheliai cells was demonstrated in vivo in melanoma metastases of patients treated with TNF and IFN-γ. These results implicate integrin αVβ3 in the anti-vascular activity of TNF and IFN-γ and demonstrate a new mechanism by which cytokines control cell adhesion.

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Affiliations

  1. Centre Pluridisciplinaire d'Oncologie (CPO), School of Medicine, University of Lausanne, Centre Hospitalier Universitaire Vaudois, c/o ISREC, 155 Chemin des Boveresses, CH-1066, Epalinges, Switzerland

    • Curzio Rüegg
    • , Aysim Yilmaz
    • , Grégory Bieler
    •  & Ferdy J. Lejeune
  2. Swiss Institute for Experimental Cancer Research (ISREC), 155 Chemin des Boveresses, CH-1066, Epalinges, Switzerland

    • Jeannine Bamat
  3. Institute of Pathology, School of Medicine, University of Lausanne, CH-1011, Lausanne, Rue du Bugnon 25, CH-1011, Lausanne, Switzerland

    • Pascal Chaubert

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https://doi.org/10.1038/nm0498-408

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