HIV-tat product is angiogenic in vivo and mimics heparin-binding angiogenic growth factors (Meeting abstract).

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HIV-tat product is angiogenic in vivo and mimics heparin-binding angiogenic growth factors (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 36:A540 1995. Unique Identifier : AIDSLINE ICDB/95608319
Albini A; Masiello L; Benelli R; Presta M; Rusnati M; Bussolino F; Soldi R; Noonan D; Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy

Abstract: Transgenic animal studies have linked expression of the HIV-tat gene to the appearance of Kaposi's sarcoma (KS)-like lesions (an angiogenic tumor associated with AIDS), and tat has been shown to be a growth factor for KS and activated endothelial cells. tat is also chemotactic for vascular cells. We have shown that recombinant HIV-tat is angiogenic in vivo using the matrigel sponge model (Albini et al, AIDS 8:1237-44, 1994). The angiogenic properties of tat at picomolar concentrations depend on the presence of heparin. Comparison of the tat sequence to that of several other angiogenic growth factors shows that its basic domain (RKKRRQRRR) is similar to the heparin binding (HB) domains of HB-growth factors. Such arg-lys rich regions are found in VEGF (RKRKKSRYK), bFGF, HGF/scatter factor, HB-EGF and the spliced, HB form of PlGF. This basic domain is in the area of substantial homology between HIV-1 tat and HIV-2 tat (RRRRTPKKTK). We have found that tat product binds to heparin columns and is eluted by high salt. The HIV-tat protein also induces tyrosine phosphorylation of specific proteins in endothelial cells, like other HB angiogenic growth factors. As found with bFGF, heparin could be involved in the angiogenic properties of tat protein, its binding to cells, uptake and intracellular transport to the nucleus.

Keywords: Amino Acid Sequence Endothelial Growth Factors/GENETICS Fibroblast Growth Factor, Basic/GENETICS Gene Products, tat/*GENETICS Heparin/METABOLISM Hepatocyte Growth Factor/GENETICS HIV-1 HIV-2 Lymphokines/GENETICS Neoplasms/*PATHOLOGY *Neovascularization, Pathologic ABSTRACT
950830
M9580996

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