Procoagulant microparticles derived from cancer cells have determinant role in the hypercoagulable state associated with cancer

Rousseau,Aurélie; Van Dreden,Patrick; Khaterchi,Amir; Larsen,Annette K.; Elalamy,Ismail; Gerotziafas,Grigoris T.

doi:10.3892/ijo.2017.4170

Procoagulant microparticles derived from cancer cells have determinant role in the hypercoagulable state associated with cancer

Authors:
- Aurélie Rousseau
- Patrick Van Dreden
- Amir Khaterchi
- Annette K. Larsen
- Ismail Elalamy
- Grigoris T. Gerotziafas
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Affiliations: Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, INSERM U938, Institut Universitaire de Cancérologie, Faculty of Medicine Pierre and Marie Curie (UPMC), Sorbonne Universities, Paris, France, Clinical Research, Diagnostica Stago, Gennevilliers, France, Department of Biological Hematology, Tenon Hospital, University Hospitals of the East Paris, Paris, France
Published online on: October 20, 2017 https://doi.org/10.3892/ijo.2017.4170
Pages: 1793-1800

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Abstract

Hypercoagulablity is a common alteration of blood coagulation in cancer patients. However, the procoagulant activity of cancer cells is not sufficient to induce hypercoagulability. The present study was aimed to identify the mechanism with which hypercoagulabilty is produced in the presence of cancer cells. We focused on the analysis of the procoagulant elements carried by cancer cell-derived microparticles (CaCe-dMP) and we evaluated the impact of microparticles associated with the cancer cells from which they stem on thrombin generation. CaCe-dMP from the cancer cells were isolated from the conditioned medium and analyzed for tissue factor (TF) and procoagulant phospholipid expression. Thrombin generation of normal plasma was assessed by the Thrombinoscope (CAT®) in the presence or absence of pancreas adenocarcinoma cells (BXPC3) or breast cancer MCF7 cells supplemented with the respective CaCe-dMP. Both BXPC3 and MCF7 cells express abundant amounts of active TF. Phosphatidylserine was identified on the surface of CaCe-dMP, unlike the cancer cells themselves. The expression of TFa by the microparticles was significantly higher to that observed on the cancer cells. Culture of the cancer cells with their microparticles resulted in thrombin generation significantly higher as compared to the upper normal limit. In conclusion, cancer cells ‘enrich’ the microenvironment with procoagulant elements, especially procoagulant microparticles which express TF and procoagulant phospholipids. The association of cancer cells with procoagulant microparticles is necessary for a state of hypercoagulability, at the level of the tumoral microenvironment. The intensity of the hypercoagulability depends on the histological type of the cancer cells.

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