Abstract
- Brain metastasis remains one of the most severe outcomes of triple-negative breast cancer (TNBC), reflecting the ability of circulating tumor cells to cross the highly restrictive brain endothelial barrier. Successful metastatic seeding requires dynamic interactions between cancer cells and brain endothelial cells that promote vascular adhesion and trans-endothelial passage.
Emerging evidence suggests that tumor-derived extracellular vesicles act as potent mediators of intercellular communication within the metastatic microenvironment. In this study, we explored whether vesicles released by highly brain-metastatic TNBC cells condition the brain endothelium to favor metastatic infiltration.
Extracellular vesicles were isolated from TNBC cell populations with distinct brain metastatic capacities and applied to brain endothelial cultures prior to functional extravasation assays. Endothelial activation and tumor cell migratory behavior were quantitatively assessed.
Our results demonstrate that vesicles originating from highly metastatic TNBC cells significantly enhanced endothelial permissiveness, leading to increased tumor cell adhesion and trans-endothelial migration. Notably, exposure to these vesicles also potentiated the invasive capacity of less aggressive TNBC cells, indicating a transferable pro-metastatic phenotype.
These findings identify extracellular vesicles as critical modulators of brain endothelial function during TNBC metastasis. Targeting vesicle-mediated endothelial reprogramming may represent a promising strategy to interfere with early metastatic events and prevent brain colonization.
Biography
Dr Rania Harati is Associate Professor at the College of Pharmacy, University of Sharjah, United Arab Emirates. She earned her PhD in Experimental and Clinical Pharmacology from Paris-Sud University (Paris-Saclay University) and completed her postdoctoral training at Pierre and Marie Curie University (Sorbonne University) in Paris, France. Her research focuses on understanding the regulation of the blood-brain barrier in health and diseas2.