ArticleOncotarget2016
Heparins that block VEGF-A-mediated von Willebrand factor fiber generation are potent inhibitors of hematogenous but not lymphatic metastasis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 3 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Synergistic effects of anticoagulants and platelet aggregation inhibitors with immune checkpoint inhibitors in cancer therapy: a comprehensive review of preclinical and clinical evidence.Journal for immunotherapy of cancer · 2026Pooled it
- Towards an emerging role for anticoagulants in cancer therapy: a systematic review and meta-analysis.Frontiers in oral health · 2024Pooled it
- Pooled it
- Shear-Activated von Willebrand Factor Captures Extracellular Vesicles to Promote Platelet Activation and Metastasis.Journal of extracellular vesicles · 2026Article
- Tumor-associated macrophages display differential protein cargo sorting in extracellular vesicles associated with poor survival in ovarian cancer.Molecular medicine (Cambridge, Mass.) · 2026Article
- A Rare But Fatal Toxicity: Immune Checkpoint Inhibitor-Related Acquired Thrombotic Thrombocytopenic Purpura.Journal of immunotherapy and precision oncology · 2025Review
- Plasma von Willebrand factor levels in patients with cancer: A meta‑analysis.Oncology letters · 2024Article
- Review
- Von Willebrand factor and hematogenous cancer metastasis under flow.Frontiers in cell and developmental biology · 2024Review
- Prognostic value of von Willebrand factor levels in patients with metastatic melanoma treated by immune checkpoint inhibitors.Journal for immunotherapy of cancer · 2023Article
- Von Willebrand factor in the plasma and in the tumor tissue predicts cancer-associated thrombosis and mortality.Haematologica · 2023Article
- Immunothrombotic Mechanisms Induced by Ingenol Mebutate Lead to Rapid Necrosis and Clearance of Anogenital Warts.International journal of molecular sciences · 2022Article
- Breast cancer cells mediate endothelial cell activation, promoting von Willebrand factor release, tumor adhesion, and transendothelial migration.Journal of thrombosis and haemostasis : JTH · 2022Article
- The role of VWF/FVIII in thrombosis and cancer progression in multiple myeloma and other hematological malignancies.Journal of thrombosis and haemostasis : JTH · 2022Review
- Article
- The Intriguing Connections between von Willebrand Factor, ADAMTS13 and Cancer.Healthcare (Basel, Switzerland) · 2022Review
- Tumor Cell-Induced Platelet Aggregation as an Emerging Therapeutic Target for Cancer Therapy.Frontiers in oncology · 2022Review
- Review
- Inflammatory cell-associated tumors. Not only macrophages (TAMs), fibroblasts (TAFs) and neutrophils (TANs) can infiltrate the tumor microenvironment. The unique role of tumor associated platelets (TAPs).Cancer immunology, immunotherapy : CII · 2021Review
- The Role of Interleukin-1-Receptor-Antagonist in Bladder Cancer Cell Migration and Invasion.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Von Willebrand factor (VWF) serves as a nidus for platelet aggregation and thrombosis. We hypothesize that VWF fibers contribute to the development of venous thromboembolism (VTE) and to metastasis formation. Here, we show that vascular and lymphatic endothelial cells (ECs) express VWF in vitro and release VWF fibers after activation by tumor cell supernatants. In contrast, an ex vivo analysis of primary mouse tumors revealed the presence of VWF fibers in the blood microvasculature but not in lymphatic vessels. Unlike the anticoagulant Fondaparinux, an inhibitor of thrombin generation, the low-molecular-weight heparin (LMWH) Tinzaparin inhibited VWF fiber formation and vessel occlusion in tumor vessels by blocking thrombin-induced EC activation and vascular endothelial growth factor-A (VEGF-A)-mediated VWF release. Intradermal tumor cell inoculation in VWF- and ADAMTS13-deficient mice did not alter lymph node metastases compared with wild type animals. Interestingly, multiple tumor-free distal organs exhibited hallmarks of malignancy-related VTE, including luminal VWF fibers, platelet-rich thrombi and vessel occlusions. Furthermore, ADAMTS13 deficiency, characterized by prolonged intraluminal VWF network lifetimes, resulted in a severely increased number of metastatic foci in an experimental model of hematogenous lung seeding. Treatment with Tinzaparin inhibited tumor-induced release of VWF multimers, impeded platelet aggregation and decreased lung metastasis. Thus, our data strongly suggest a critical role of luminal VWF fibers in determining the occurrence of thrombosis and cancer metastasis. Moreover, the findings highlight LMWHs as therapeutic strategy to treat thrombotic complications while executing anti-metastatic activities.
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Registered trials
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