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

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.

Field of science

  • /medical and health sciences/medical biotechnology/genetic engineering/gene therapy
  • /medical and health sciences/clinical medicine/oncology/cancer

Call for proposal

ERC-2009-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Address
Batiment Ce 3316 Station 1
1015 Lausanne
Switzerland
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 969 258,08
Principal investigator
Michele De Palma (Dr.)
Administrative Contact
Caroline Vandevyver (Ms.)

Beneficiaries (2)

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Switzerland
EU contribution
€ 969 258,08
Address
Batiment Ce 3316 Station 1
1015 Lausanne
Activity type
Higher or Secondary Education Establishments
Principal investigator
Michele De Palma (Dr.)
Administrative Contact
Caroline Vandevyver (Ms.)
FONDAZIONE CENTRO SAN RAFFAELE DEL MONTE TABOR

Participation ended

Italy
EU contribution
€ 342 641,92
Address
Via Olgettina 60
20132 Milano
Activity type
Research Organisations
Administrative Contact
Maria Guttinger (Ms.)