INFLAMET

Mechanistic insights into the impact of tumor-associated neutrophils on metastatic breast cancer

 Coordinatore STICHTING HET NEDERLANDS KANKER INSTITUUT 

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 Nazionalità Coordinatore Netherlands [NL]
 Totale costo 1˙999˙360 €
 EC contributo 1˙999˙360 €
 Programma 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)
 Code Call ERC-2013-CoG
 Funding Scheme ERC-CG
 Anno di inizio 2014
 Periodo (anno-mese-giorno) 2014-03-01   -   2019-02-28

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    STICHTING HET NEDERLANDS KANKER INSTITUUT

 Organization address address: PLESMANLAAN 121
city: AMSTERDAM
postcode: 1066 CX

contact info
Titolo: Dr.
Nome: Henri
Cognome: Van Luenen
Email: send email
Telefono: +31 205122097
Fax: +31 206691383

NL (AMSTERDAM) hostInstitution 1˙999˙360.00
2    STICHTING HET NEDERLANDS KANKER INSTITUUT

 Organization address address: PLESMANLAAN 121
city: AMSTERDAM
postcode: 1066 CX

contact info
Titolo: Dr.
Nome: Karina Elizabeth
Cognome: De Visser
Email: send email
Telefono: +31 205126104
Fax: +31 205122057

NL (AMSTERDAM) hostInstitution 1˙999˙360.00

Mappa


 Word cloud

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spontaneous    tumor    neutrophils    function    samples    neutrophil    mouse    data    immune    largely    disease    model    patients    pathways    unexplored    metastasis    metastatic    breast    models    pro    cancer   

 Obiettivo del progetto (Objective)

'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.'

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