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Impacts of antithrombotic agents on cellular physiology in the pancreatic tumoral environment

1Clinical Research Department, Diagnostica Stago, Gennevilliers, France.; Sorbonne Université, INSERM UMR_S938, Research Group « Cancer-Hemostasis-Angiogenesis », Centre de Recherche Saint-Antoine, Institut Universitaire de Cancérologie, Paris, France., Gennevilliers, Ile-de-France, France, 2Diagnostica Stago, Gennevilliers, France., Gennevilliers, Ile-de-France, France, 3Sorbonne Université, INSERM UMR_S938, Research Group « Cancer-Hemostasis-Angiogenesis », Centre de Recherche Saint-Antoine, Institut Universitaire de Cancérologie, Paris, France., Paris, Ile-de-France, France, 4Thrombosis and Haemostasis Centre, Biological Hematology Department, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris (AP-HP), Sorbonne Université, Paris, France.; Department of Obstetrics and Gynecology, I M Sechenov First Moscow State Medical University, Moscow, Russia, Paris, Ile-de-France, France, 5Sorbonne Université, INSERM UMR_S938, Research Group « Cancer-Hemostasis-Angiogenesis », Centre de Recherche Saint-Antoine, Institut Universitaire de Cancérologie, Paris, France ; Thrombosis and Haemostasis Centre, Biological Hematology Department, Hôpital Tenon, Assistance Pu-blique-Hôpitaux de Paris (AP-HP), Sorbonne Université, Paris, France., Paris, Ile-de-France, France

Abstract Number: VPB0577

Meeting: ISTH 2022 Congress

Theme: Coagulation and Natural Anticoagulants » Coagulation Factors and Inhibitors

Background: Antithrombotic agents (AG) potentially exert an inhibition of the procoagulant properties of tumoral microenvironment and interfere with cancer cell biology, but this has been inadequately studied so far.

Aims: To investigate the role of LMWHs and the specific factor Xa inhibitors apixaban and fondaparinux on the procoagulant potential and physiology of pancreatic cancer cell line BXPC3 and their microenvironment.

Methods: BXPC3 cells were exposed to either enoxaparin, tinzaparin (2 anti-Xa UI/ml), fondaparinux (2 µg/ml), or apixaban (2 µg/ml) for 48h. The procoagulant properties of BXPC3 and their conditioned media (CM) were then assessed with the Calibrated Automated Thrombogram®. The viability of BXPC3 was tested with the MTT assay. mRNA expression of Tissue Factor (TF), Vascular Endothelial Growth Factor (VEGF), and Thrombospondin 1 (THSB1) was evaluated by RT-qPCR. Residual concentrations of the AG in the conditioned media was measured with specific anti-Xa amidolytic assays.

Results: Exposure to apixaban resulted in significant decrease of TF mRNA expression and a significant increase of that of THBS1. Fondaparinux and enoxaparin resulted in significant decrease of mRNA expression of VEGF. Cell viability was reduced by enoxaparin (14%), tinzaparin (11%), fondaparinux (12%), and apixaban (30%). AG did not significantly modify the impact of BXPC3 cells on thrombin generation but significantly impaired that capacity of the CM. Exposure to BXPC3 induced a significant decrease of the concentration of fondaparinux (27%), enoxaparin (48%) and tinzaparin (26%) in the CM, but did not significantly impact that of apixaban.

Conclusion(s): AG interfere with tumoral microenvironment not only by impairing the pro-coagulant properties of cancer cells’ secretome, but also by altering cell viability, and gene expression of pro- and antiangiogenic factors VEGF and THBS1. Nonetheless, a degradation of LMWH and fondaparinux was observed after two days of exposure to cancer cells. Apixaban escaped of any deteriorating effect of cancer cells and preserved its antithrombotic potency.

To cite this abstract in AMA style:

Tran H, Van Dreden P, Mbemba E, Elalamy I, Gerotziafas G. Impacts of antithrombotic agents on cellular physiology in the pancreatic tumoral environment [abstract]. https://abstracts.isth.org/abstract/impacts-of-antithrombotic-agents-on-cellular-physiology-in-the-pancreatic-tumoral-environment/. Accessed September 29, 2023.

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