ED394 - www.ed394.upmc.fr

ED394 - www.ed394.upmc.fr
16/03/2017
Unité de recherche : Centre de Recherche Saint-Antoine (UMR_S 938)
Equipe de recherche : Biologie et Thérapeutiques du Cancer (Cancer Biology and Therapeutics)
Groupe d'Accueil de Doctorants : Modulation de l'hypercoagulabilité plasmatique et cellulaire par les cance
Directeur de thèse porteur du projet : M. GEROTZIAFAS Grigorios ([email protected])
Co-encadrant(e) :
Nombre de doctorants accueillis dans l'équipe en 2016/2017 : 1
Nombre de doctorants encadrés par le porteur de projet / par le co-encadrant : 2 / 0
Unité : Centre de Recherche Saint-Antoine
Équipe : Biologie et Thérapeutiques du Cancer (Cancer Biology and Therapeutics)
GAD : Modulation de l'hypercoagulabilité plasmatique et cellulaire par les cance
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ED394 - www.ed394.upmc.fr
16/03/2017
Titre du sujet de thèse : Modelisation of the procoagulant properties of cancer cells with their microenvironment
during the vasculogenic mimicry process
Résumé du sujet :
Cancer is a leading cause of venous thromboembolism (VTE) and vice versa. Pulmonary embolism is the second
cause of death in cancer patients and the risk of VTE is about 7-fold higher in cancer patients as compared to
patients without cancer. The pathogenesis of thrombosis during cancer is particularly complex stemming from
multiple connections of this disease with both systems of inflammation and hemostasis. Angiogenesis is an
essential process for cancer progression which also implicates activation of platelets and blood coagulation
mechanism. Cancer cells promote activation of blood coagulation mainly through the expression of tissue factor
(TF), the major trigger of blood coagulation process, on the tumor cell surface. Tumor TF expression has been
documented in numerous cancer types, including colorectal cancer cells.
Tumor progression is associated with coagulation activation. In addition to its procoagulant role, TF expression is
linked with the activation of intracellular pathways leading to cell migration, proliferation and angiogenesis. Some
cancer cells are capable of forming new vascular network independently of the angiogenic process of endothelial
cells. This process, called Vasculogenic Mimicry (VM) is associated with phenotypic changes of cancer cells which
acquire some "endothelial - like" properties. Cancer cells entering into the VM process form new "vessels" from the
tumor towards pre-existent vessels. Thus, they are able to receive nutriments and oxygen and are involved into the
neoangiogenic and metastatic process. The elucidation of the molecular mechanisms of the VM process starts to
attract the interest of several research groups.
Cancer cells entering at VM process and forming "vascular-like" network are in contact with blood flow and
theoretically should possess some regulatory properties equilibrate the procoagulant and anticoagulant forces of
the blood in order to enhance angiogenesis and to prevent blood coagulation. The mechanism by which cancer
cells at VM status modify their microenvironment and interact with blood coagulation system and platelets has not
been investigated yet. This domain is of major interest for both the coprehension of cancer dissemination process
and for the identification of new therapeutic targets.
The central aim of the project is to investigate central aspects of the mechanism by which cancer cells interact with
platelets, endothelial cells, monocytes and blood coagulation components when they enter in VM status.
To address these questions the project aims to investigate
1. the expression of TF by cancer cells before and after formation of the vascular network
2. the release of procoagulant microparticles and natural coagulation inhibitors by cancer cells at steady state and
at VM status.
3. the alterations platelets, white blood cells and coagulation system during their interactions with cancer cells at
VM status
Our laboratory has set up an experimental system for the
Unité : Centre de Recherche Saint-Antoine
Équipe : Biologie et Thérapeutiques du Cancer (Cancer Biology and Therapeutics)
GAD : Modulation de l'hypercoagulabilité plasmatique et cellulaire par les cance
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ED394 - www.ed394.upmc.fr
16/03/2017
Projet ouvert à la mobilité : Non
Candidat(e) préssenti(e) sur le projet : Aucun
Projet présenté pour le concours d'attribution des contrats doctoraux 2017 : Oui
Autre(s) financement(s) demandé(s) et/ ou prévu(s) : Non
Cotutelle : Non
Collaboration en interface : Non
Accord pour la publication sur le site Web de l'Ecole Doctorale : Oui
Unité : Centre de Recherche Saint-Antoine
Équipe : Biologie et Thérapeutiques du Cancer (Cancer Biology and Therapeutics)
GAD : Modulation de l'hypercoagulabilité plasmatique et cellulaire par les cance
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