Inserm, Institut national de la santé et de la recherche médicale
Faculté de pharmacie, Aix Marseille Université

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Cellular and molecular mechanisms involved in thrombosis associated with a cancer, tumor growth and metastasis

Grants from ANR-JCJC and the ARC association.

This project is performed by a CR1 INSERM (Laurence Panicot-Dubois).

Since its first clinical description in 1865 by Armand Trousseau, the association between thrombosis and cancer has been extensively documented. Venous Thromboembolism (VTE) including both deep vein thrombosis (DVT) and pulmonary embolism (PE) occurs in 15% to 20% of patients suffering from a cancer. This disease constitutes one of the main cause of death during the evolution of the cancer and represents a major therapeutic problem.

During the evolution of a tumor a procoagulant/thrombotic phenotype takes place conferring numerous advantages to the cancer cells. Indeed, both the activation of the coagulation cascade and the aggregation of blood platelets around cancer cells protect themselves from the immune response, facilitate their circulation in the bloodstream and their adhesion at potential sites of metastasis.

Therapeutic treatments with anticoagulant or antithrombotic drugs may thus act on both the procoagulant state and the development of the tumor. The goal of this study is to determine in dedicated mouse models, the role played by platelets and cancer-cell derived microparticles on thrombosis, development of the tumors and formation of metastasis.

Our current results indicate that cancer cell-derived microparticles constitute the main source of Tissue Factor involved in thrombosis associated with cancer (Thomas GM, JEM, 2009). The activation of circulating platelets is playing an important role for tumor growth and formation of metastasis (Mezouar et al., submitted). These preliminary results confirm our main hypothesis and show that inhibition of platelet activation is an interesting pathway to diminish both the size of the tumor and the coagulopathy.

Now, we would like to confirm these results in murine orthotopic models of cancer and to identify the molecular mechanisms linking platelet activation and tumor growth.

Main publications on this topic : Thomas GM et al., JEM, 2009. Panicot-Dubois L. et al., JCI, 2007.