Tinzaparin inhibits VEGF-A–mediated angiogenesis in primary skin tumors and impedes tumor cell metastasis. Tumor-bearing mice were treated with vehicle (A; control) or tinzaparin (B) and cryosections of primary tumors were analyzed by immunofluorescences for CD31. Morphometric quantification of the vessel density (C) demonstrates a significant difference in vessel density upon tinzaparin treatment compared with control tumors. Quantitative assessment of vessels in tinzaparin-treated tumors (D) shows that tinzaparin treatment results in a significant increase of small vessels (<50 µm) and decrease of big vessels (>150 µm). Plots show mean ± SD (n = 4-6 animals of 2 independent experiments; scale bar = 100 µm; *P < .05). Schematic overview shows the role of tumor cell-mediated EC activation in cancer progression (E-G). Circulating tumor cells secrete VEGF (E) followed by activation of endothelial cells and the release of procoagulatory VWF fibers (F). VWF mediates platelet aggregation and tumor cell binding, promoting extravasation (G). Binding of the LMWH tinzaparin blocks VEGF-mediated angiogenesis and VWF release attenuating tumor progression (H).