Reduced ADAMTS13 activity in tumor tissue promotes intraluminal VWF fiber formation in tumor microvessels. Immunofluorescence staining of cryosections for VWF (green), platelets (red), and the endothelial cell marker CD31 (red). DNA was stained with DAPI (blue). Mouse melanoma cells (Ret) were injected intradermally and mice were treated with recombinant ADAMTS13 (rADAMTS13; E-F) or 0.9% NaCl (C-D) as control. Reconstitution of ADAMTS13 reduced the formation of intraluminal ULVWF networks and platelet aggregation compared with vehicle treatment. In comparison with wild-type skin (A-B), less VWF in the vessel wall indicates ULVWF degradation after exocytosis (n = 5-6 animals; scale bars = 20 µm). To analyze the impact of ADAMTS13 on VWF fiber formation, vessels with or without luminal fibers were quantified. Infusion with rADAMTS13 significantly decreased the number of vessels with ULVWF (G). The activity and the protein expression of ADAMTS13 in tumor tissue were significantly reduced compared with healthy skin measured by a FRET-based assay and western blot (H; n = 3-5 animals, *P < .05, **P < .005). See also supplemental Table 2.