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Phenotypic characterization of Liver-derived exosomes populations associated with liver metastasis in pancreatic cancers

Objective

Tumors are not isolated entities, but complex systemic networks involving cell-cell communication between transformed and non-transformed cells. The milieu created by tumor-associated cells may either support or halt tumor progression. Non-tumor cells also play a role at distant sites, preparing future metastatic sites to support engraftment and survival of metastatic cells. In addition to cell-cell contact, cells communicate through secreted factors via a highly complex system involving characteristics such as ligand concentration, receptor expression and integration of diverse signaling pathways. Of these, extracellular vesicles such as exosomes are emerging as novel cell-cell communication players in physiological and pathological scenarios. We recently described that exosomes produced by highly metastatic pancreatic cancers (PC) induce Liver Pre-Metastatic Niches (LPMN) supportive of hepatic metastasis. Although we defined how LPMN are induced by PC-derived exosomes, the specific mechanism of how the LPMN support the formation and progression of liver metastatic lesions is still unknown. In addition, while we have been showing that pre-metastatic niches support metastatic spreading, we still do not have appropriate means to detect the formation of these niches by non-invasive methods in clinical settings. Thus we propose to: 1)Characterize the composition of liver-derived exosomes populations in physiologic and LPMN-associated settings by applying state-of-the-art flow cytometry tailored to nanoparticles analysys at a single-exosome level; 2)Test whether liver-derived exosomes interact with metastatic PC cells and play a role in supporting the progression of PC metastatic lesions in the liver. This project has the potential to offer not only a non-invasive alternative to detect and characterize tumor-associated microenvironments, such as LPMN, but also opportunities for novel therapeutic approaches to target pro-tumorigenic cell-cell communication.

Fields of science (EuroSciVoc)

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Programme(s)

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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.

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.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2016

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Coordinator

FUNDACAO D. ANNA DE SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Net EU contribution

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.

€ 160 635,60
Address
AVENIDA BRASILIA, CENTRO DE INVESTIGACAO DA FUNDACAO CHAMPALIMAUD
1400-038 LISBOA
Portugal

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Total cost

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.

€ 160 635,60
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