METANICHE

Anjali Kusumbe
Investigadora Responsável
Nome

Regulation of bone metastases by age-associated angiocrine signals

Acrónimo METANICHE
Tipo de ERC Starting Grant (StG), ERC-2019-STG
Ano 2019
Valor atribuído 1,5 M€
Unidade I&D MIA, UC

Resumo

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.
Início 2019-01-01
Fim 2026-03-31
Website https://cordis.europa.eu/project/id/805201