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 language | English |
|---|---|
| Pages (from-to) | 19-26 |
| Number of pages | 8 |
| Journal | Microvascular Research |
| Volume | 63 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2002 |
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Keywords
- Endothelium
- FGF-2
- HIV-1 Tat
- Kaposi's sarcoma
ASJC Scopus subject areas
- Biochemistry
- Cardiology and Cardiovascular Medicine
Cite this
Differential response to Tat and FGF-2 of two novel clonal populations derived from murine Kaposi-like lesions developing in Tat transgenic mice. / Wu, Zhihao; Mariotti, Massimo; Cavallaro, Ugo; Soria, Marco R.; Maier, J. A M.
In: Microvascular Research, Vol. 63, No. 1, 2002, p. 19-26.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential response to Tat and FGF-2 of two novel clonal populations derived from murine Kaposi-like lesions developing in Tat transgenic mice
AU - Wu, Zhihao
AU - Mariotti, Massimo
AU - Cavallaro, Ugo
AU - Soria, Marco R.
AU - Maier, J. A M
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Endothelium
KW - FGF-2
KW - HIV-1 Tat
KW - Kaposi's sarcoma
UR - http://www.scopus.com/inward/record.url?scp=0036354791&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036354791&partnerID=8YFLogxK
U2 - 10.1006/mvre.2001.2361
DO - 10.1006/mvre.2001.2361
M3 - Article
C2 - 11749069
AN - SCOPUS:0036354791
VL - 63
SP - 19
EP - 26
JO - Microvascular Research
JF - Microvascular Research
SN - 0026-2862
IS - 1
ER -