Thrombospondin-1 inhibits Kaposi's sarcoma (KS) cell and HIV-1 Tat-inducedangiogenesis and is poorly expressed in KS lesions

Kaposi's sarcoma (KS), a neoplasm often associated with iatrogenic and acqu ired immunosuppression, is characterized by prominent angiogenesis. Angioge nic factors released by both KS and host cells, as Hell as HHV-8 and HIV vi ral products, have been implicated in the pathogenesis of this lesion. Angi ogenesis is the result of imbalance among angiogenesis promoters and inhibi tors, which disrupts homeostasis. The aim of this study. was to investigate the expression and mechanism of KS control of thrombospondin-1 (TSP), a ph ysiological inhibitor of angiogenesis. Immunohistochemical analysis of four KS lesions showed only spotty. reactivity for TSP in the stroma and in les s than 10 per cent of lesional blood vessels. In addition, the typical KS s pindle cells were not stained. In agreement with these findings, decreased levels of TSP Here measured with an ELISA assay in the supernatants of cult ured KS cells, compared with endothelial cells. In vitro, TSP inhibited the endothelial cell proliferation and motility induced by KS cell supernatant s, TSP also prevented endothelial cell motility induced by Tat, a product o f HIV-1 endowed with angiogenic potential and implicated in the pathogenesi s of AIDS-KS. In vivo, TSP inhibited the angiogenic activity exerted by Tat in the Matrigel sponge model. These results suggest that TSP down-regulati on might be permissive far the development of KS-associated angiogenesis, C opyright (C) 1999 John Wiley & Sons, Ltd.