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DLL4-LVN

Targeting the (pre)metastatic lympho-vascular niche: molecular mechanisms and therapeutic implications in melanoma

Total Cost €

0

EC-Contrib. €

0

Partnership

0

Views

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 DLL4-LVN project word cloud

Explore the words cloud of the DLL4-LVN project. It provides you a very rough idea of what is the project "DLL4-LVN" about.

thin    complete    mechanisms    lecs    dll4    belgium    ligand    homing    unclear    lymphatic    cnio    phenomenon    notch    regulates    driving    express    prognosis    abolishment    urged    wiring    me    sentinel    cancer    tumor    genetic    embo    nodes    signaling    lec    metastasis    melanoma    bec    deaths    undergo    responsible    chloroquine    lymphangiogenesis    kul    angiogenesis    niche    inactivated    vasculature    activated    blood    data    correlate    arrival    apparently    tolerance    levels    sln    trapped    gt    therapeutic    angiogenic    agostinis    actively    recruitment    pharmacologically    questions    dynamic    lysosomotropic    lesions    fellowship    mechanistic    mediators    route    soengas    compartment    outgrowth    student    lab    showing    lymphovascular    phd    endosomal    patient    interference    lymph    cell    mm    cq    preliminary    blunt    crosstalk    90    versus    pending    spain    outcome    agent    revealed    metastatic    cells    unexpected    normalizing    endothelial    establishment    immune    strategy   

Project "DLL4-LVN" data sheet

The following table provides information about the project.

Coordinator
FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III 

Organization address
address: CALLE MELCHOR FERNANDEZ ALMAGRO 3
city: MADRID
postcode: 28029
website: www.cnio.es

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Spain [ES]
 Total cost 158˙121 €
 EC max contribution 158˙121 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-01-01   to  2018-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III ES (MADRID) coordinator 158˙121.00

Map

 Project objective

Tumor metastasis is responsible for >90% of cancer deaths. A tumor type where the mechanisms driving this process are especially unclear is melanoma, the only cancer where apparently thin lesions (2 mm depth) have a high potential for metastatic dissemination. As a PhD student in P. Agostinis lab (KUL, Belgium) I identified a new strategy using the lysosomotropic agent chloroquine (CQ) to blunt melanoma metastasis, by normalizing the angiogenic vasculature via increased blood endothelial cell (BEC) NOTCH signaling. The complete abolishment of metastasis by CQ urged me to study whether another route of metastasis; the lymphatic system and the sentinel lymph nodes (SLN); was also affected. The importance of this route of metastasis is supported by recent evidence showing that even before the arrival of the tumor cells, the lymph endothelial cells (LEC) and immune cells in the SLN undergo dynamic changes that actively facilitate tumor cell recruitment, metastatic outgrowth and immune tolerance. This phenomenon is referred to as the ‘lymphovascular (pre)metastatic niche’. Pending questions are how the cancer cells, LEC and immune cells crosstalk and how to target them pharmacologically. My preliminary data, obtained during a short term EMBO Fellowship in the lab of M. Soengas (CNIO, Spain) show that CQ affects lymphangiogenesis even more than angiogenesis. These effects are due to an unexpected different wiring of the NOTCH pathway in BEC versus LEC. Activated LECs express high levels of the NOTCH ligand DLL4, which is trapped and inactivated in the endosomal compartment by CQ. Genetic interference in LEC revealed that DLL4 not only regulates lymphangiogenesis, but also the production of mediators of cancer cell homing and immune tolerance. In this project I will address the mechanistic role of DLL4 in the establishment of the lymphovascular niche, correlate DLL4 levels with melanoma patient prognosis and target DLL4 pharmacologically to improve therapeutic outcome.

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The information about "DLL4-LVN" are provided by the European Opendata Portal: CORDIS opendata.

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lastchecktime (2024-03-01 7:40:31) correctly updated