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Extracellular Vesicles as mediators of Pre-Metastatic Niche Formation in Melanoma

Objective

Every 2 minutes someone in the world is diagnosed with melanoma, so by the time you read this application dozens of new melanoma cases will be detected. Beyond its growing incidence, cutaneous melanoma is the most aggressive type of skin cancer and notorious for its high metastatic propensity, which constitutes the primary cause of death for these patients. Cellular heterogeneity and plasticity are key features of melanoma, supporting disease progression. The host laboratory has recently charted a functional map of the melanoma ecosystem and identified a cell population that fuels tumor growth (pre-EMT) and another that functions as metastasis-initiating cells (MICs). Increasing evidence indicates that metastatic dissemination of MICs relies on the formation of favourable microenvironments, or pre-metastatic niches (PMN), at secondary sites, and that extracellular vesicles (EVs) shed by the primary tumour are key mediators of PMN formation. I hypothesize that EVs produced by phenotypically distinct melanoma cells are likely to contain different biological information, and thus may exert different (possibly diverging) roles in PMNs formation. In METMAP, I will (i) determine the melanoma cell state(s) contributing to the formation of PMNs via EVs; (ii) dissect the molecular mechanisms underlying PMN formation; and (iii) unravel how these mechanisms facilitate metastatic spreading. I will leverage my background in EVs biology and establish melanoma cell state-reporters to track EV-mediated communication between melanoma subpopulations and PMNs. Proximity labelling will be used to dissect the bioactive contents of EVs transferred to PMNs and perturbation experiments will be conducted to decipher this complex interplay. Through METMAP, I will deliver a functional understanding of how distinct melanoma states contribute to the development of PMN and, ultimately, identify new targets for disruptive therapies that hinder melanoma metastasis.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

VIB VZW
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.

€ 175 920,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
Links
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.

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