Assessment of breast cancer progression and metastasis during a hypercoagulable state induced by silencing of antithrombin in a xenograft mouse model. Issue 221 (January 2023)

• Record Type: Journal Article
• Authors: Buijs, J.T.; Ünlü, B.; Laghmani, E.H.; Heestermans, M.; van Vlijmen, B.J.M.; Versteeg, H.H.
• Is Part Of: Thrombosis research. Issue 221(2023)
• Page Start: 51
• Page End: 57
• Publication Date: 2023-01
• Subjects: Breast cancer -- Metastasis -- Antithrombin -- Cancer-associated thrombosis -- Mouse model; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2022.11.018
• Languages: English
• ISSNs: 0049-3848

Abstract

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. 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