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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine oncology skin cancer melanoma
- medical and health sciences basic medicine immunology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2015
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
28029 Madrid
Spain
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.