Proteomics

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


ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cerebral Cortex Endothelial Cell, Mature Astrocyte, Cerebral Cortex, Blood-brain Barrier, Mature Microglial Cell

DISEASE(S): Brain Cancer,Breast Cancer

SUBMITTER: Sara Busatto  

LAB HEAD: Marsha Moses

PROVIDER: PXD053436 | Pride | 2025-05-07

REPOSITORIES: Pride

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Publications

Breast Cancer-Derived Extracellular Vesicles Modulate the Cytoplasmic and Cytoskeletal Dynamics of Blood-Brain Barrier Endothelial Cells.

Busatto Sara S   Song Tzu-Hsi TH   Kim Hyung Joon HJ   Hallinan Caleb C   Lombardo Michael N MN   Stemmer-Rachamimov Anat O AO   Lee Kwonmoo K   Moses Marsha A MA  

Journal of extracellular vesicles 20250101 1


Extracellular vesicles (EVs) from brain-seeking breast cancer cells (Br-EVs) breach the blood-brain barrier (BBB) via transcytosis and promote brain metastasis. Here, we defined the mechanisms by which Br-EVs modulate brain endothelial cell (BEC) dynamics to facilitate their BBB transcytosis. BEC treated with Br-EVs show significant downregulation of Rab11fip2, known to promote vesicle recycling to the plasma membrane and significant upregulation of Rab11fip3 and Rab11fip5, which support structu  ...[more]

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