Involvement of vascular endothelial growth factor in Kaposi's sarcoma associated with acquired immunodeficiency syndrome.

To examine the role of vascular endothelial growth factor (VEGF) in the development of edema associated with Kaposi's sarcoma (KS) in acquired immunodeficiency syndrome (AIDS), we exploited animal model systems to detect the activity that induces vascular hyper-permeability (VHP) using cultured AIDS-KS spindle cells. Cultured AIDS-KS spindle cells and conditioned medium (AIDS-KS-CM) that had been semi-purified through a heparin affinity column were tested for the ability to induce VHP in animals. The AIDS-KS spindle cells and AIDS-KS-CM induced VHP that was histamine-independent. The VHP-inducing activity was detected in the 0.5 M NaCl fraction from the heparin affinity column and was blocked by anti-VEGF neutralizing antibody. In addition, the production of VEGF was demonstrated in fresh AIDS-KS tissue as well as in cultured AIDS-KS cells, while control cells were negative for VEGF production. From these observations, we concluded that AIDS-KS cells produce a factor(s) that promotes VHP, and this factor could be VEGF.