Project Inflammation-induced niche remodelling in controlling melanoma dormancy

Basic data

Title:
Inflammation-induced niche remodelling in controlling melanoma dormancy
Duration:
01/06/2021 to 31/05/2024
Abstract / short description:
Circulating neutrophils are an independent marker of poor prognosis in melanoma patients. We propose that in an inflammatory environment neutrophil influx and neutrophil extracellular trap (NET) release induces a signal reprogramming in dormant melanoma cells. This is mediated by remodeling of extracellular matrix (ECM) components in the niche by NET components, which induces an epithelial to mesenchymal (EMT)-transition in the melanoma cells promoting their dissemination. Furthermore, we propose that in a non-inflammatory environment a therapy with DNA damaging agents induces a release of extracellular DNA by dying tumor or endothelial cells in the niche, that activates distinct signal pathways different from those induced by NETs such as cGAS/STING signaling, which results in maintenance of tumor dormancy. We will analyze the effect of different extracellular matrix components as well as endothelial and immune cells in the niche on induction, maintenance or reawakening of cell cycle arrest using our recently established in vitro melanoma dormancy model. We will analyze the crosstalk of endothelial cells, immune cells and melanoma cells in the niche and its effect on the dormant state. Finally, we will validate our results in suitable in vivo models using also patient-derived disseminated melanoma cells.
Keywords:
melanoma dormancy
neutrophils

Involved staff

Managers

Department of Dermatology
Hospitals and clinical institutes, Faculty of Medicine

Local organizational units

Department of Dermatology
Hospitals and clinical institutes
Faculty of Medicine

Funders

Bonn, Nordrhein-Westfalen, Germany
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