Obiettivo Metastatic disease is still largely unexplored, poorly understood and incurable. Accumulating evidence indicates that cells and mediators of the immune system can facilitate metastasis. Neutrophil accumulation in cancer patients has been associated with metastasis formation. In mouse tumor models, neutrophils have been reported to be pro- or anti- metastatic, but the underlying mechanisms involved in either function remain largely elusive. This proposal outlines a research program aimed at resolving the pro-metastatic role of neutrophils in breast cancer, as our preliminary data indicate that neutrophils proactively mediate breast cancer metastasis. Using a state-of-the art spontaneous breast cancer metastasis mouse model, we will mechanistically study how neutrophils facilitate metastasis formation and how mammary tumors provoke the metastasis-facilitating function of neutrophils. Building upon my previous studies and our current data, we will focus on the unexplored crosstalk between the adaptive immune system and neutrophils in facilitating spontaneous metastatic disease. These crucial questions will be addressed by undertaking a multidisciplinary approach, involving sophisticated mouse models for metastatic breast cancer, RNA sequencing on tumor-associated neutrophil populations, state-of-the-art mouse engineering, intravital imaging and in vivo neutrophil manipulations. Moreover, we will validate our findings from the mouse metastasis model in human breast cancer samples. We will determine the metastasis predicting power of the identified murine pro-metastatic neutrophil-specific pathways by immunohistochemistry and multi-parameter immunofluorescence on breast cancer samples and blood of untreated patients of which clinical follow-up is available. Thus, we will identify novel molecular pathways that can be targeted to selectively inhibit the pro-metastatic activity of the immune system. Campo scientifico medical and health sciencesbasic medicineimmunologymedical and health sciencesclinical medicineoncologybreast cancernatural sciencesbiological sciencesgeneticsRNA Programma(i) 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) Argomento(i) ERC-CG-2013-LS6 - ERC Consolidator Grant - Immunity and Infection Invito a presentare proposte ERC-2013-CoG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-CG - ERC Consolidator Grants Istituzione ospitante STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS Contributo UE € 1 999 360,00 Indirizzo PLESMANLAAN 121 1066 CX Amsterdam Paesi Bassi Mostra sulla mappa Regione West-Nederland Noord-Holland Groot-Amsterdam Tipo di attività Research Organisations Contatto amministrativo Henri Van Luenen (Dr.) Ricercatore principale Karina Elizabeth De Visser (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS Paesi Bassi Contributo UE € 1 999 360,00 Indirizzo PLESMANLAAN 121 1066 CX Amsterdam Mostra sulla mappa Regione West-Nederland Noord-Holland Groot-Amsterdam Tipo di attività Research Organisations Contatto amministrativo Henri Van Luenen (Dr.) Ricercatore principale Karina Elizabeth De Visser (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato