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Assessment of breast cancer progression and metastasis during a hypercoagulable state induced by silencing of antithrombin in a xenograft mouse model

  • J.T. Buijs
    Affiliations
    Einthoven Laboratory for Vascular and Regenerative Medicine, Division of Thrombosis and Hemostasis, Department of Medicine, Leiden University Medical Centre, Leiden, the Netherlands
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  • B. Ünlü
    Affiliations
    Einthoven Laboratory for Vascular and Regenerative Medicine, Division of Thrombosis and Hemostasis, Department of Medicine, Leiden University Medical Centre, Leiden, the Netherlands
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  • E.H. Laghmani
    Affiliations
    Einthoven Laboratory for Vascular and Regenerative Medicine, Division of Thrombosis and Hemostasis, Department of Medicine, Leiden University Medical Centre, Leiden, the Netherlands
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  • M. Heestermans
    Affiliations
    Einthoven Laboratory for Vascular and Regenerative Medicine, Division of Thrombosis and Hemostasis, Department of Medicine, Leiden University Medical Centre, Leiden, the Netherlands
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  • B.J.M. van Vlijmen
    Affiliations
    Einthoven Laboratory for Vascular and Regenerative Medicine, Division of Thrombosis and Hemostasis, Department of Medicine, Leiden University Medical Centre, Leiden, the Netherlands
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  • H.H. Versteeg
    Correspondence
    Corresponding author.
    Affiliations
    Einthoven Laboratory for Vascular and Regenerative Medicine, Division of Thrombosis and Hemostasis, Department of Medicine, Leiden University Medical Centre, Leiden, the Netherlands
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Published:November 24, 2022DOI:https://doi.org/10.1016/j.thromres.2022.11.018

      Highlights

      • Cancer results in increased risk for venous thrombosis
      • Effect of venous thrombosis on cancer progression remains unclear
      • In mice, induction of a hypercoagulable state did not influence breast cancer progression

      Abstract

      Local coagulation activation has been shown to impact both primary tumor growth and metastasis in mice. It is well known that components of the blood clotting cascade such as tissue factor and thrombin play a role in tumor progression by activating cellular receptors and local formation of fibrin. However, whether venous thromboembolism (VTE) or a hypercoagulable state has a direct impact on cancer progression is unknown. Here we have combined an orthotopic murine breast cancer model, using female Nod-SCID mice, with siRNA-mediated silencing of antithrombin (siAT) leading to the induction of a systemic hypercoagulable state. We show that, compared to control siRNA-treated (not experiencing a hypercoagulable state) tumor-bearing mice, siAT treated tumor-bearing mice do not show enhanced tumor growth nor enhanced metastasis. We conclude that, in this murine model for hypercoagulability, induction of a hypercoagulable state does not contribute to breast cancer progression.

      Keywords

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