VASCULAR ENDOTHELIAL GROWTH-FACTOR IS A POTENT ANGIOGENIC FACTOR IN AIDS-ASSOCIATED KAPOSIS-SARCOMA-DERIVED SPINDLE CELLS

Angiogenesis is one of the most important features of AIDS-associated Kaposi's sarcoma (AIDS-KS), Our studies suggested that spindle-shaped AIDS-KS cells from various AIDS-KS lesions play important roles in the development of KS lesions, Basic fibroblast growth factor (bFGF) has been reported to be a predominant angiogenic factor expressed in AIDS- KS cells, However, our data from ELISA revealed the presence of the va scular endothelial growth factor (VEGF) molecule in large quantities i n AIDS-KS cell-derived conditioned medium (AIDS-KS-CM) (12.1-21.4 ng/m l), In contrast, small amounts of bFGF were detected in AIDS-KS-CM (76 -245 pg/ml). The combination of anti-VEGF and anti-bFGF IgGs completel y inhibited endothelial cell growth-promoting activities in AIDS-KS-CM , while activities partially remained in the presence of anti-bFGF IgG or anti-VEGF IgG alone, VEGF and bFGF in AIDS-KS-CM were distinguishe d by heparin-affinity chromatography, Furthermore, the combination of VEGF and bFGF synergistically augmented the growth of endothelial cell s. Both VEGF and bFGF revealed an angiogenic property that was inhibit ed by specific Abs, when applied to the rabbit cornea and chicken chor ioallantoic membrane, On Western blots, anti-VEGF IgG gave two major b ands of 22 and 24 kDa, similar to those of recombinant VEGF(165). As d etected on Northern blots, AIDS-KS cells expressed major 3.9-kb VEGF-s pecific mRNA. Thus, VEGF, in concert with bFGF, may play a crucial rol e in the angiogenesis of AIDS-KS lesions.