Kaposi's sarcoma cells of different etiologic origins respond to HIV-Tat through the flk-1/KDR (VEGFR-2): Relevance in AIDS-KS pathology

Kaposi's sarcoma (KS) is an hyperplastic lesion whose main histological fea tures are typical spindle shaped cells with a mixed endothelial-mesenchymal -macrophage phenotype, an intense vascularization and an inflammatory infil trate. The etiology of KS appears to be linked to activation of a latent HH V8 infection. Sporadic and iatrogenic KS are slow progressing lesions that can undergo spontaneous regression. In contrast, KS, which is frequently as sociated with HIV infection, is found in a highly aggressive form in AIDS p atients. The HIV-1 Tat has been shown to activate the VEGF receptor KDR in endothelial and KS spindle cells, suggesting this HIV protein could contrib ute to KS pathogenesis. We used primary 'reactive' KS cell culture from spo radic and epidemic KS, and an immortal KS-line (KS-Imm) isolated in our lab oratory from a iatrogenic KS lesion, to verify if Tat-induced cell signalin g is able to mediate cellular responses. We demonstrate that KS cells migra ted in response to Tat and that VEGF is able to compete with the Tat chemot actic activity towards these cells. A function-blocking anti-KDR antibody w as able to abrogate both VEGF and Tat-induced KS chemotactic response, indi cating a direct involvement of this receptor. Our data show that HIV-Tat ca n also activate KS cells derived from sporadic or iatrogenic lesions, sugge sting that in AIDS patients Tat could cooperate with VEGF in activation of KDS on KS precursor spindle and endothelial cells, and contribute to the ag gressiveness of AIDS-KS lesions. (C) 2000 Academic Press.