Activation of CD40 favors the growth and vascularization of Kaposi's sarcoma

Although CD40 is expressed by several tumor lines and is up-regulated in tu mor vascular endothelium, its role in tumor biology is still unclear. In th e present study, we investigated the role of CD40 in the growth and vascula rization of Kaposi's sarcoma (KS), In vitro, stimulation of CD40 induced mi gration of KS cells and inhibited vincristine-induced apoptosis, Similarly, the CD40 engagement on endothelial cells resulted in cell contraction, mig ration, and prevention of serum withdrawal-apoptosis. To understand the bio logical relevance of CD40 in vivo, KS cells were engineered to express and release a soluble form of CD40 (KS-sCD40) able to disrupt CD40-CD154 intera ction. SCID mice s.c. injected with KS-sCD40 cells developed tumors that we re significantly smaller than those induced by control cells (KS-neo), In a ddition, KS-sCD40 tumors showed several areas of necrosis, diffuse presence of apoptotic cells, and poor vascularization. In contrast, KS-neo tumors s howed few or absent areas of necrosis and apoptosis and intense vasculariza tion: Moreover, anti-CD40 Abs stimulated neo-angiogenesis in a murine model in which s.c, implantation of Matrigel was used as a vehicle for the deliv ery of mediators. These observations provide demonstration that CD40 suppor ts tumor cell survival, growth, and neo-vascularization of KS.