Evidence map›Paper›PMID 25977583›Full record

ArticleBlood2015

von Willebrand factor fibers promote cancer-associated platelet aggregation in malignant melanoma of mice and humans.

Alexander T Bauer, Jan Suckau, Kathrin Frank, Anna Desch, Lukas Goertz, Andreas H Wagner, Markus Hecker, Tobias Goerge, Ludmila Umansky, Philipp Beckhove and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 2 pooled it
9.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 158 citations in OpenAlex.

  1. Pooled it
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  3. Trial
  4. Trial
  5. Role of comorbidities and medication on immunotherapy efficacy in cSCC: A DeCOG multicentre analysis.Journal of the European Academy of Dermatology and Venereology : JEADV · 2026
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  12. Von Willebrand disease: A century of progress.Research and practice in thrombosis and haemostasis · 2026
    Review
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  18. Article
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21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 2 countries.

Alexander T BauerExperimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;
Jan SuckauExperimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;
Kathrin FrankSkin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany;
Anna DeschExperimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;
Lukas GoertzExperimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;
Andreas H WagnerInstitute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany;
Markus HeckerInstitute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany;
Tobias GoergeDepartment of Dermatology, University of Muenster, Muenster, Germany;
Ludmila UmanskyDepartment of Translational Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany; and.
Philipp BeckhoveDepartment of Translational Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany; and.
Jochen UtikalSkin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany;
Christian GorzelannyExperimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;
Nancy Diaz-ValdesSkin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany; Division of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra, Pamplona, Spain.
Viktor UmanskySkin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany;
Stefan W SchneiderExperimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;
Heidelberg University · DEGerman Cancer Research Center · DEUniversity Hospital Heidelberg · DEUniversity Medical Centre Mannheim · DEUniversity of Münster · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumor-mediated procoagulatory activity leads to venous thromboembolism and supports metastasis in cancer patients. A prerequisite for metastasis formation is the interaction of cancer cells with endothelial cells (ECs) followed by their extravasation. Although it is known that activation of ECs and the release of the procoagulatory protein von Willebrand factor (VWF) is essential for malignancy, the underlying mechanisms remain poorly understood. We hypothesized that VWF fibers in tumor vessels promote tumor-associated thromboembolism and metastasis. Using in vitro settings, mouse models, and human tumor samples, we showed that melanoma cells activate ECs followed by the luminal release of VWF fibers and platelet aggregation in tumor microvessels. Analysis of human blood samples and tumor tissue revealed that a promoted VWF release combined with a local inhibition of proteolytic activity and protein expression of ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type I repeats 13) accounts for this procoagulatory milieu. Blocking endothelial cell activation by the low-molecular-weight heparin tinzaparin was accompanied by a lack of VWF networks and inhibited tumor progression in a transgenic mouse model. Our findings implicate a mechanism wherein tumor-derived vascular endothelial growth factor-A (VEGF-A) promotes tumor progression and angiogenesis. Thus, targeting EC activation envisions new therapeutic strategies attenuating tumor-related angiogenesis and coagulation.

Indexed as

Platelet AggregationADAM ProteinsADAMTS13 ProteinAnimalsBlood CoagulationBlood PlateletsDisease Models, AnimalDisease ProgressionEndothelial CellsEnzyme ActivationFibrinolytic AgentsHeparin, Low-Molecular-WeightHumansMelanomaMiceMice, TransgenicADAM ProteinsADAMTS13 ProteinADAMTS13 protein, humanFibrinolytic AgentsHeparin, Low-Molecular-WeightProto-Oncogene Proteins c-retTinzaparinVascular Endothelial Growth Factor Avon Willebrand Factor

Identifiers

PMID25977583
PMCPMC4432010
OpenAlexW1546771217

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.