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DLL4-LVN
Targeting the (pre)metastatic lympho-vascular niche: molecular mechanisms and therapeutic implications in melanoma
Total Cost €
0EC-Contrib. €
0Partnership
0Views
0DLL4-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.
bec
apparently
mechanisms
vasculature
levels
establishment
driving
phenomenon
mm
student
agostinis
lymphatic
endothelial
responsible
lymphovascular
homing
inactivated
angiogenic
phd
crosstalk
strategy
endosomal
cancer
undergo
dynamic
agent
gt
unexpected
pending
lysosomotropic
complete
trapped
activated
sentinel
soengas
wiring
blunt
express
angiogenesis
route
cnio
cell
versus
prognosis
mechanistic
lymphangiogenesis
normalizing
tumor
spain
ligand
sln
showing
actively
genetic
urged
compartment
embo
fellowship
correlate
90
me
blood
lecs
regulates
preliminary
questions
notch
recruitment
revealed
lec
nodes
chloroquine
lab
outcome
tolerance
data
metastatic
immune
cells
arrival
therapeutic
lymph
mediators
dll4
unclear
pharmacologically
belgium
melanoma
signaling
outgrowth
thin
cq
metastasis
niche
lesions
abolishment
deaths
kul
interference
patient
Project "DLL4-LVN" data sheet
The following table provides information about the project.
| Coordinator |
FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 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 (2024-07-27 1:53:31) correctly updated