Objective 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. Fields of science medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesclinical medicineoncology Keywords Tumor angiogenesis Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS7 - Applied life sciences, biotechnology and bioengineering: agricultural, animal, fishery, forestry/food sciences; biotechnology, chemical biology, genetic engineering, synthetic biology, industrial biosciences; environmental biotechnology. Call for proposal ERC-2009-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Address Batiment ce 3316 station 1 1015 Lausanne Switzerland See on map Region Schweiz/Suisse/Svizzera Région lémanique Vaud Activity type Higher or Secondary Education Establishments Principal investigator Michele De Palma (Dr.) Administrative Contact Caroline Vandevyver (Ms.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution € 969 258,08 Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Switzerland EU contribution € 969 258,08 Address Batiment ce 3316 station 1 1015 Lausanne See on map Region Schweiz/Suisse/Svizzera Région lémanique Vaud Activity type Higher or Secondary Education Establishments Principal investigator Michele De Palma (Dr.) Administrative Contact Caroline Vandevyver (Ms.) Links Contact the organisation Opens in new window Website Opens in new window FONDAZIONE CENTRO SAN RAFFAELE DEL MONTE TABOR Participation ended Italy EU contribution € 342 641,92 Address Via olgettina 60 20132 Milano See on map Region Nord-Ovest Lombardia Milano Activity type Research Organisations Administrative Contact Maria Guttinger (Ms.) Links Contact the organisation Opens in new window Website Opens in new window
