Overexpression of thrombospondin-1 decreases angiogenesis and inhibits thegrowth of human cutaneous squamous cell carcinomas

The function of the endogenous angiogenesis inhibitor thrombospondin-1 (TSP -1) in epithelial tumor development has remained controversial. We studied the ill vitro growth characteristics and the in vivo tumor xenograft growth of the human squamous cell carcinoma cell lines A431 and SCC-13, stably tr ansfected to overexpress human TSP-1. Overexpression of TSP-1 inhibited tum or growth of A431 xenotransplants, and completely abolished tumor formation by SCC-13 cells. TSP-1 overexpressing A431 tumors were characterized by ex tensive areas of necrosis and by decreased tumor vessel number and size. Th e effects of TSP-1 on tumor cell growth Fc ere indirect since tumor cell pr oliferation rates in vivo and in vitro, anchorage-dependent and -independen t growth in vitro, and susceptibility to induction of apoptosis by serum wi thdrawal were unchanged in TSP-1 overexpressing tumor cells. However, TSP-1 overexpression up-regulated the TSP-1 receptor CD36, leading to enhanced a dhesion of A431 cells to TSP-1. These findings establish TSP-1 as a potent inhibitor of angiogenesis and tumor growth in carcinomas of the skin.