TUMOR SPHEROID-INDUCED VESICLE FORMATION ON ENDOTHELIAL-CELLS IS ASSOCIATED WITH PROCOAGULANT PROPERTIES

Fibrin deposits in tumor beds are an intriguing phenomenon. It has bee n suggested that fibrin plays a role as a provisional matrix in which the tumor grows and induces development of a vascular network. On the other hand fibrin possibly protects the tumor nodule from host defense mechanisms. We therefore investigate whether tumor cells can induce a procoagulant response in endothelial cells leading to fibrin formatio n. For our studies we employed a modification of the matrix model of M ontesano in which sprouting of endothelial cell aggregates can be foll owed. This system allows us to study in vitro the involvement of coagu lation in tumor growth and angiogenesis. Cocultures of endothelial cel l aggregates and avascular tumor spheroids in collagen type I gels res ults in the appearance of extracellular vesicle-like structures on the endothelial sprouts. The vesicles formed on endothelial cell sprouts upon coculturing with tumor cells exhibit an increased amidolytic acti vity, suggestive of factor X/Xa activity, not dependent on tissue fact or exposure. Experiments using HgCl2 and Iodoacetamide point to the im portance of SH groups in the factor X/Xa activity on endothelial cell sprouts.