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Contribution de la TSP-1 dans l "hémostase, l" angiogénèse et la dissémination métastatique

Ziel

As a newly recruited scientist my project aims at validate the strategy consisting in the neutralization of thrombospondin-1 (TSP-1) as a pharmacological approach for the treatment of thrombosis, and for the development of an anti-cancer therapy based on t he properties of TSP-1 in metastasis and angiogenesis. In close collaboration with my postdoctoral host, we will study the contribution of TSP-1 in platelet recruitment onto vessel wall, in vivo, with the use of TSP-1 null mice in models of inflammation an d thrombosis monitored in situ by intravital videomicroscopy; bone marrow transplantation between wild type and TSP-1-/- mice; in vitro, with the identification of cell-receptors of TSP-1 important for platelet adhesion and aggregation. Platelets are favouring metastasis by participating in tumour cells adhesion and extravasations through the vessel wall. Since TSP-1 is a major platelet component, we will investigate its role in platelets/tumour cells/endothelium interactions.

The work will be conduced in WT and TSP-1-/- mice; by tracking platelets/tumour cells conjugates interacting with the endothelium using intra vital microscopy. Because cancer is often associated with inflammation and thrombosis, which, in turn, favour metastasis, we will use in vivo and in vitro models to study the role of TSP-1 in these processes TSP-1 is an anti-angionegic protein. However the N-ter TSP-1 fragment is pro-angiogenic. Using both in vitro and in vivo models, we will evaluate whether the production of the fragment correlates with the extent of angiogenesis, and whether its neutralization is an efficient anti-angiogenic strategy for anti-cancer therapy. I initiated the creation in the reintegration host, of a structure operating the in vivo models that I developed during my pos t-doc. The structure will be used to complete my project and will be utilized as a shared facility to encourage collaborative works within the institute and to attract collaborators from outside.

Wissenschaftliches Gebiet (EuroSciVoc)

Thema/Themen

Aufforderung zur Vorschlagseinreichung

FP6-2002-MOBILITY-11
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

ERG - Marie Curie actions-European Re-integration Grants

Koordinator

INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCH MÉDICALE
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