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Regulation of bone metastases by age-associated angiocrine signals

Project description

Breaking new ground in bone, blood and age-related diseases

What is the link between vascular ageing and bone metastasis? Using cutting-edge techniques like advanced 3D and 4D bone imaging, the EU-funded METANICHE project aims to answer this question. It will also employ cell-specific inducible mouse genetics, transcriptional profiling and bioinformatics. The project’s aim is to define the role of highly promising novel candidate age-related angiocrine signals with sophisticated inducible endothelial-specific humanised mouse models. Expected to break new ground by unravelling a repertoire of age-related angiocrine factors, the findings will contribute to a wider scientific community in bone, blood and age-related diseases. The project will contribute to the development of therapeutic strategies for targeting dormant tumour cells in bones.

Objective

Blood vessels form a versatile transport network and provide inductive signals called angiocrine factors to regulate tissue-specific functions. Blood vessels in bone are heterogeneous with distinct capillary subtypes that exhibit remarkable alterations with age. Bone is the most prevalent site of metastasis, and ageing is linked to the reactivation of dormant tumor cells (dorTCs) and metastatic relapse. Bone remodeling processes are also associated with metastatic relapse. Here, I will define the role of distinct vascular niches in regulating the fate of DTCs in bone. Finally, I will unravel the age-related angiocrine factors and identify key angiocrine signals that drive the reactivation of dorTCs. I will employ a powerful combination of advanced 3D, intravital, and whole body imaging, cell specific-inducible mouse genetics, transcriptional profiling and bioinformatics in an unprecedented manner to achieve my goals. New cutting-edge techniques such as advanced 3D and 4D bone imaging are important aspects of my proposal. I will also define the role of highly promising novel candidate age-related angiocrine signals with sophisticated inducible endothelial-specific humanised mouse models. My work will break new ground by unraveling a repertoire of age-related angiocrine factors and will contribute to a wider scientific community in bone, blood, and age-related diseases. This interdisciplinary work at the frontiers of bone, cancer and vascular biology will provide the first conceptual link between vascular ageing and bone metastasis and will contribute towards the development of therapeutic strategies for targeting DTCs in bone.

Fields of science (EuroSciVoc)

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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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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2018-STG

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Host institution

UNIVERSIDADE DE COIMBRA
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.

€ 741 854,65
Address
PACO DAS ESCOLAS
3004-531 COIMBRA
Portugal

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Activity type
Higher or Secondary Education Establishments
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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.

€ 741 854,65

Beneficiaries (2)

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