Inhibition of angiogenesis by type I interferons in models of Kaposi's sarcoma

C. Marchisone, R. Benelli, A. Albini, L. Santi, D. M. Noonan

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Kaposi's Sarcoma (KS) is a pathology which occurs with increased frequency and in a particularly aggressive form in AIDS patients. The HIV-1 Tat protein appears to be an important co-factor in the induction of the extensive neo-vascularization associated with AIDS-KS. Tat acts as a chemoattractant for endothelial cells in vitro, inducing both chemotactic and invasive responses. Several clinical trials have been performed testing the effectiveness of diverse biological agents in therapy of KS, among these the type I interferons. Type I IFNs have diverse biological functions besides their anti-viral activity, including anti-angiogenic properties. We have shown that IFNα and IFNβ are potent inhibitors of both primary and immortalized endothelial cell migration and morphogenesis in vitro as well as neo-angiogenesis induced by HIV-I Tat in vivo. The inhibitory effect of IFN class I on HIV-Tat associated angiogenesis further supports its use as a therapy for epidemic Kaposi's sarcoma. The use of recombinant IFNs at the levels required to obtain a therapeutic effect are associated with side effects and toxicity, therefore we are now developing a gene therapy approach for constant and local delivery type I IFNs.

Original languageEnglish
Pages (from-to)257-262
Number of pages6
JournalInternational Journal of Biological Markers
Volume14
Issue number4
Publication statusPublished - Oct 1999

Fingerprint

Interferon Type I
Kaposi's Sarcoma
Endothelial cells
tat Gene Products
Gene therapy
Chemotactic Factors
Biological Factors
Pathology
Toxicity
HIV-1
Acquired Immunodeficiency Syndrome
Endothelial Cells
Human Immunodeficiency Virus tat Gene Products
Testing
Therapeutic Uses
Morphogenesis
Genetic Therapy
Cell Movement
Clinical Trials
HIV

Keywords

  • Angiogenesis
  • HIV Tat
  • Interferon
  • Kaposi's sarcoma

ASJC Scopus subject areas

  • Immunology
  • Biochemistry

Cite this

Inhibition of angiogenesis by type I interferons in models of Kaposi's sarcoma. / Marchisone, C.; Benelli, R.; Albini, A.; Santi, L.; Noonan, D. M.

In: International Journal of Biological Markers, Vol. 14, No. 4, 10.1999, p. 257-262.

Research output: Contribution to journalArticle

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AB - Kaposi's Sarcoma (KS) is a pathology which occurs with increased frequency and in a particularly aggressive form in AIDS patients. The HIV-1 Tat protein appears to be an important co-factor in the induction of the extensive neo-vascularization associated with AIDS-KS. Tat acts as a chemoattractant for endothelial cells in vitro, inducing both chemotactic and invasive responses. Several clinical trials have been performed testing the effectiveness of diverse biological agents in therapy of KS, among these the type I interferons. Type I IFNs have diverse biological functions besides their anti-viral activity, including anti-angiogenic properties. We have shown that IFNα and IFNβ are potent inhibitors of both primary and immortalized endothelial cell migration and morphogenesis in vitro as well as neo-angiogenesis induced by HIV-I Tat in vivo. The inhibitory effect of IFN class I on HIV-Tat associated angiogenesis further supports its use as a therapy for epidemic Kaposi's sarcoma. The use of recombinant IFNs at the levels required to obtain a therapeutic effect are associated with side effects and toxicity, therefore we are now developing a gene therapy approach for constant and local delivery type I IFNs.

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