Beta interferon inhibits HIV-1 Tat-induced angiogenesis: Synergism with 13-cis retinoic acid

M. Iurlaro, R. Benelli, L. Masiello, M. Rosso, L. Santi, A. Albini

Research output: Contribution to journalArticle

Abstract

Kaposi's sarcoma (KS) is a highly angiogenic lesion which frequently presents as an aggressive form in HIV-infected male patients. We have previously shown that the HIV-1 Tat protein induces endothelial cell migration and invasion in vitro and a rapid angiogenic response in vivo, suggesting that it acts as a cofactor in epidemic KS. In this study we tested beta interferon (IFNβ) and retinoic acid (RA) for the inhibition of Tat- induced angiogenesis using in vivo and in vitro models. IFNβ, at a concentration above 2500 U/ml, was an effective inhibitor of Tat-stimulated growth, migration and morphogenesis of an endothelial cell line in vitro and of angiogenesis in vivo. A strong reduction of properties associated with neovascularisation was induced by 10 000 U/ml. In vivo, RA alone was on ineffective inhibitor of angiogenesis, and in vitro gave only a limited inhibition of endothelial cell growth. However, 13-cis RA used in combination with IFNβ impressively potentiated its effects. A combination of lower doses of IFNβ (2500 U/ml) and 13-cis RA induced a virtually complete inhibition of the Tat-related angiogenic phenotype both in vivo and in vitro. The potentiation of the anti-angiogenic activity of IFNβ by 13-cis RA suggests that this combination could be a useful approach for the therapy of epidemic KS.

Original languageEnglish
Pages (from-to)570-576
Number of pages7
JournalEuropean Journal of Cancer
Volume34
Issue number4
DOIs
Publication statusPublished - Mar 1998

Keywords

  • Angiogenesis
  • HIV-1
  • Interferon
  • Retinoids
  • Tat

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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