Differential response to Tat and FGF-2 of two novel clonal populations derived from murine Kaposi-like lesions developing in Tat transgenic mice

Zhihao Wu, Massimo Mariotti, Ugo Cavallaro, Marco R. Soria, J. A M Maier

Research output: Contribution to journalArticlepeer-review

Abstract

Kaposi's sarcoma (KS), a highly vascularized multifocal tumor frequent and aggressive in HIV-infected individuals, is initiated and maintained by the concomitant action of HIV-1 Tat, cytokines, and growth factors. Spindle cells, the proliferative component of KS lesions, were isolated from Kaposi-like lesions developing in Tat transgenic mice and cloned. Here we describe the behavior of two of the clones obtained: cells from clone 1 showed the classical endothelial phenotype and were therefore named murine endothelial cells (MEC), while cells from clone 2 had a typical spindle shape, coexpressed markers of endothelial, smooth muscle, and macrophage lineage; and were named spindle cells (SC). Tat stimulated MEC growth and migration, but not uPA production, suggesting that Tat cannot activate a complete angiogenic program in these cells, unless FGF-2 is present. Tat stimulated SC growth only when the cells were cultured at low density and this correlated with the induction of tyrosine phosphorylation of various substrates, among which was erk-2, which mediates mitogenic signaling. The inhibition of SC growth in high cell density culture by Tat could be circumvented by the addition of FGF-2. We conclude that (i) the response of SC to Tat is density dependent and (ii) the angiogenic effect of Tat on both MEC and SC requires the presence of FGF-2.

Original languageEnglish
Pages (from-to)19-26
Number of pages8
JournalMicrovascular Research
Volume63
Issue number1
DOIs
Publication statusPublished - 2002

Keywords

  • Endothelium
  • FGF-2
  • HIV-1 Tat
  • Kaposi's sarcoma

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine

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