Home   >   PhD topics   >   2016


Back to search form

Role of blood platelets in metastatic dissemination

Research unit

UMR_S 949 - Biologie et pharmacologie des plaquettes sanguines : hémostase, thrombose, transfusion (BPPS)
10, rue Spielmann - BP 36 67065 Strasbourg Cedex


Name: Biologie et pharmacologie des plaquettes

Group leader: GACHET Christian - christian.gachet@efs.sante.fr

Group leader's phone: 0388212525

Website: Visit website

Group organization:
- Chercheurs: 4
- ITA: 8
- Doctorants: 2
- Post-Docs: 2
- Autres: 2

Publications of the team linked to the topic (3 last years):
1) Platelets in cancer. From basic research to therapeutic implications. Mammadova-Bach E, Mangin P, Lanza F, Gachet C.Hamostaseologie. 2015;35(4):325-36.
2) Platelet glycoprotein VI binds to polymerized fibrin and promotes thrombin generation. Mammadova-Bach E, Ollivier V, Loyau S, Schaff M, Dumont B, Favier R, Freyburger G, Latger-Cannard V, Nieswandt B, Gachet C, Mangin PH, Jandrot-Perrus M.Blood. 2015 Jul 30;126(5):683-91.
3) Integrin α6β1 is the main receptor for vascular laminins and plays a role in platelet adhesion, activation, and arterial thrombosis. Schaff M, Tang C, Maurer E, Bourdon C, Receveur N, Eckly A, Hechler B, Arnold C, de Arcangelis A, Nieswandt B, Denis CV, Lefebvre O, Georges-Labouesse E, Gachet C, Lanza F, Mangin PH. Circulation. 2013 Jul 30;128(5):541-52.

About PhD

PhD Director: MANGIN Pierre - pierre.mangin@efs.sante.fr

Phone: 0687922254

Junior advisor: non

Co-tutely: non

Co-Director: non

About PhD topic :

Title: Role of blood platelets in metastatic dissemination

Project: During cancer progression, tumor cells acquire survival, proliferative and invasive properties which lead to their dissemination and metastasis formation. Metastasis is the main cause of mortality in patients suffering from cancer. Cells detach from the primary tumor, enter into the bloodstream where they interact with platelets. Blood platelets are small anucleated cells playing a key role in the arrest of bleeding. In addition, they are also involved in non-hemostatic functions including metastatic dissemination. It has notably been reported that patients with a breast or colon cancer exhibit an elevated platelet count, called thombocytosis, which represents a bad prognosis. Several in vitro studies showed that platelets directly interact with tumor cells through a mechanism that remains to be established. Several hypotheses were proposed concerning this interaction which could allow cancer cells to escape immune surveillance and be protected from shear stress, recruit these cells at the endothelium, allow their transmigration or regulate their functions at distant sites.
The aim of this phD proposal is to unravel the mechanisms by which platelets participate in metastatic dissemination of breast and colon cancer. To do so, we will use models based on orthotopic injection of breast (E0771) and colon (MC38) cancer cells. Tumor growth and metastatic formation will be followed over time by bioluminescence imaging on the whole mouse body. Anatomopathological properties of the metastasis will be determined by histological methods. The role of platelets will be evaluated with antiplatelet agents (aspirine, clopidrogel) and we will determine the role of several platelet receptors (β1 integrins, P2Y1, P2X1, GPVI…) by using genetically modified mice available in our animal facility. In addition to this in vivo work, we will use numerous human and mouse cancer cell lines (MCF7, SKRB3, E0771…) to study in vitro and ex vivo their physical and functional interaction with platelets. These experiments will be performed in suspension (flow cytometry) and static and flow conditions. Finally, intravital microscopy (confocal microscopy) will be used to visualize in mice (mesenteric arterioles and skin fold chamber) the interactions between platelets, tumor cells and endothelial cells, as well as the role of platelets in tumor cell extravasation.The perspectives of this work are to better understand the role of platelets in metastatic formation and to propose novel anticancer strategies.

Wished skills: Dynamic, highly motivated and elevated scientific rigor. General knowledge in cellular biology.

Expertises which will be acquired during the training: Expertise in the field of platelet physiology and cancer. Technical expertise in imaging, cellular biology and various animal models of metastasis