Abstract
Brain metastasis from breast cancer (BMBC) contributes significantly to mortality, yet its mechanisms remain unclear. This study investigates the activation of GPX3+ astrocytes by circulating tumor cell (CTC)-derived exosomes in the metastatic process. Using a mouse model of BMBC, we performed single-cell RNA sequencing (scRNA-seq) and metabolomics to explore the role of GPX3+ astrocytes in the brain microenvironment. We found that CTCs activate these astrocytes, promoting IL-1β production and Th17 cell differentiation, crucial for the formation of the metastatic niche. Conditional knockout of GPX3 reduced brain metastasis and extended survival, highlighting its importance in metastasis. Our findings uncover a novel mechanism by which CTCs activate GPX3+ astrocytes to drive breast cancer brain metastasis, suggesting new therapeutic targets for intervention.