Rita Banga

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Description

Brain metastases (BrM) in breast cancer are associated with poor survival, and neutrophil extracellular traps (NETs) have emerged as key drivers of tumor migration and invasion. This study explores how BrM cells sense and respond to NETs via CCDC25, a membrane-localized extracellular DNA sensor. Using a polyacrylamide-based hydrogel co-culture system, we spatially segregated tumor cells and neutrophils while preserving their biochemical interactions. Our findings reveal that CCDC25 expression is significantly upregulated in BrM cells in response to NETs, leading to enhanced tumor invasion. Notably, tumor migration was directly proportional to NET density, with cells aligning toward NET-rich regions, particularly when collagen was introduced to facilitate migration. Additionally, BrM tumors appear to reprogram neutrophils to generate NETs in the surrounding stroma, reinforcing a pro-metastatic microenvironment. The study suggests that NET-stroma interactions serve as key regulators of BrM tumor dynamics, promoting directional migration and invasion. These insights provide a mechanistic understanding of how NET sensing facilitates BrM progression, highlighting CCDC25-NET interactions as potential therapeutic targets for metastatic breast cancer

Publication Date

4-1-2025

Keywords

Neutrophils, CCDC25, Tumor, Invasion

Neutrophil Extracellular Traps Sensing Activates Directional Migration of Brain Metastatic Breast Tumors

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