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Contenido archivado el 2024-06-18

Tie2-expressing monocytes: Role in tumor angiogenesis and therapeutic targeting

Objetivo

Recent data indicated that tumor-infiltrating myeloid cells promote tumor angiogenesis. We contributed to this concept by showing that Tie2-expressing monocytes (TEMs) have a requisite role in this process. Indeed, the specific elimination of TEMs inhibits tumor angiogenesis and growth in several models. Yet, little is known of the biological bases of TEMs activity in tumors. Building upon my previous studies, I will provide a thorough characterization of the precise identity of TEMs and of their biological role in mouse tumor models. I will perform comparative gene expression studies and analyze the developmental relationship between TEMs and other monocyte-lineage cells. By exploiting state-of-the-art genetic strategies, including novel gene knockdown platforms and exogenously- and microRNA-regulated vectors, I will identify and validate molecular pathways that may be targeted to selectively inhibit TEMs activity in tumors. I recently showed that TEMs can be turned into efficient and therapeutically effective vehicles for the targeted delivery of interferon-alpha to tumors. I will now implement preclinical models, including human hematochimeric mice, that will better assess the safety and feasibility of this new delivery strategy. Finally, I will assess the relevance of TEMs in metastasis, and exploit them to constrain metastatic dissemination and growth, either by a cell depletion approach or by delivering interferon specifically at the metastatic niche. The results of these studies will increase significantly our knowledge of the biological functions of proangiogenic monocytes in tumor development, and may improve cancer therapies by enlightening novel and yet unrecognized therapeutic targets and by providing proof-of-feasibility of a new gene therapy strategy.

Palabras clave

Convocatoria de propuestas

ERC-2009-StG
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Régimen de financiación

ERC-SG - ERC Starting Grant

Institución de acogida

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Aportación de la UE
€ 969 258,08
Dirección
BATIMENT CE 3316 STATION 1
1015 Lausanne
Suiza

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Región
Schweiz/Suisse/Svizzera Région lémanique Vaud
Tipo de actividad
Higher or Secondary Education Establishments
Investigador principal
Michele De Palma (Dr.)
Contacto administrativo
Caroline Vandevyver (Ms.)
Enlaces
Coste total
Sin datos

Beneficiarios (2)