Breast cancer-derived extracellular vesicles modulate the cytoplasmic metabolism and cytoskeletal mechanics of blood-brain barrier endothelial cells

Normal cerebral vasculature is characterized by high selectivity, low permeability and low transcytosis rates, ensuring proper brain physiology. Our group has demonstrated that extracellular vesicles isolated from brainseeking MDA-MB-231 cells (Br-EVs) breach the intact BBB in vivo and significantly increase the incidence of breast-to-brain metastasis, suggesting a dysfunction of the cerebral microvasculature. To elucidate the mechanisms by which Br-EVs modify the BBB and promote breast-to-brain metastasis, we utilized a quantitative global proteomic approach to assess changes in protein expression within murine cerebral microvessels post-Br-EV treatment. We employed label-free mass spectrometry-based quantitative proteomics to analyze the protein content of cerebral microvessels from the brains of mice treated with PBS, P-EVs or Br-EVs.