Differential response to Tat and FGF-2 of two novel clonal populations derived from murine Kaposi-like lesions developing in Tat transgenic mice.
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.
Wu
Zhihao
Z
Università di Milano, DISP Vialba, Via G. B. Grassi, 74 Milan, Italy.
Mariotti
Massimo
M
Cavallaro
Ugo
U
Soria
Marco R
MR
Maier
Jeanette A M
JA
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000502:physiology; D015696:Gene Products, tat / Q000235:genetics* / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D011233:Precipitin Tests; D012514:Sarcoma, Kaposi / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D015696:Gene Products, tat; D016222:Fibroblast Growth Factor 2; D014443:Tyrosine; D014568:Urokinase-Type Plasminogen Activator