VPB0577 - Impacts of antithrombotic agents on cellular physiology in the pancreatic tumoral environment

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Co-Author(s)

Huong Chi Mai Tran, MSc

Clinical 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
PV

Patrick Van Dreden

PhD clinical research manager
Clinical Research Department, Diagnostica Stago
Gennevilliers, Ile-de-France, France
EM

Elisabeth Mbemba

biology engineer
Sorbonne 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
IE

Ismail Elalamy

Professor of Hematology
Thrombosis 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

Presenting Author(s)

GG

Grigorios Gerotziafas

Professor of Hematology
Sorbonne 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

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.