Objectif Primary cancers can induce lymphatic vessel growth (lymphangiogenesis), enhancing metastasis to draining lymph nodes (LNs). We found that tumors also induce lymphangiogenesis in draining LNs, leading to increased cancer spread to distal LNs and beyond. Very recently, we found that lymphatic vessel activation in peripheral tissues and draining LNs also plays a previously unanticipated role in the control of chronic inflammatory diseases. This proposal aims at a comprehensive characterization of the function of lymphatic vessels in inflammation, using a variety of genetic mouse models for enhanced or reduced lymphatic function, novel quantitative techniques for the in vivo imaging of lymphatic function, and a miniaturized 3-dimensional in vitro platform for the high-throughput phenotypic screening of libraries of small, drug-like molecules for modulators of lymphatic function. A genome-wide analysis of the gene expression profile shall be made from lymphatic vessels isolated by high-speed cell sorting and by immuno-laser capture microdissection from tumors and their lymph node metastases, inflamed tissue and its draining lymph nodes, and normal tissues, followed by functional characterization of potential therapeutic targets and diagnostic markers. Finally, we will establish novel genetically fluorescent mouse models for the in vivo real-time imaging of lymphatic activation, and we will develop an innovative approach for the in vivo detection of early micrometastases, using antibody-based PET and near-infrared imaging of tumor-induced stromal changes. These studies will improve our understanding of lymphatic involvement in inflammation and cancer metastasis, and will provide the basis for completely novel approaches to treat and detect inflammation and cancer metastasis. Champ scientifique medical and health scienceshealth sciencesinflammatory diseasesmedical and health sciencesclinical medicineoncology 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) Thème(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Appel à propositions ERC-2010-AdG_20100317 Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Contribution de l’UE € 2 493 300,00 Adresse Raemistrasse 101 8092 Zuerich Suisse Voir sur la carte Région Schweiz/Suisse/Svizzera Zürich Zürich Type d’activité Higher or Secondary Education Establishments Contact administratif Michael Johannes Detmar (Prof.) Chercheur principal Michael Johannes Detmar (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Suisse Contribution de l’UE € 2 493 300,00 Adresse Raemistrasse 101 8092 Zuerich Voir sur la carte Région Schweiz/Suisse/Svizzera Zürich Zürich Type d’activité Higher or Secondary Education Establishments Contact administratif Michael Johannes Detmar (Prof.) Chercheur principal Michael Johannes Detmar (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
