Endothelial cell (EC) activation is a prerequisite for tumor spreading and angiogenesis. One initial step
of EC activation includes the exocytosis of Weibel-Palade bodies (WPBs), followed by the release of the
procoagulatory protein von Willebrand factor (VWF) and inflammatory cytokines. Although WPBs are
also present in lymphatic ECs (LEC), their regulation, function and composition are unknown. This
proposal focuses on tumor cell-induced WPB exocytosis in ECs (including LECs), VWF release and its
impact on tumor cell adhesion and spreading within the lymphatic vessels.