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Related Experiment Video

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Author Spotlight: Studying Brain Endothelial Barrier in Metastatic Cancer Using Impedance-Based Biosensors
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Heparan Sulfate Modulation Affects Breast Cancer Cell Adhesion and Transmigration across In Vitro Blood-Brain

Yunfei Li1, David B Shteyman1, Zeina Hachem2

  • 1Department of Biomedical Engineering, The City College of the City University of New York, New York, NY 10031, USA.

Cells
|January 26, 2024
PubMed
Summary

Vascular endothelial growth factor (VEGF) differentially affects heparan sulfate (HS) on blood-brain barrier (BBB) cells and breast cancer cells, influencing metastasis. Targeting HS may offer a therapeutic strategy for brain metastasis.

Keywords:
MDA-MB-231blood–brain barrierglycocalyxheparinase IIImatrix metalloproteinase (MMP) inhibitororosomucoidsphingosine-1-phosphate (S1P)vascular endothelial growth factor (VEGF)

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Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Endothelial heparan sulfate (HS) disruption is crucial for tumor cell metastasis.
  • VEGF reduces HS on blood-brain barrier (BBB) cells but increases it on breast cancer cells (MB231).

Purpose of the Study:

  • To investigate if VEGF's differential HS effect promotes MB231 adhesion and transmigration across the BBB.
  • To determine if agents enhancing endothelial HS can reduce MB231 adhesion and transmigration.

Main Methods:

  • Generated an in vitro BBB model using human cerebral microvascular endothelial cells (hCMECs).
  • Quantified HS levels on BBB and MB231 cells after treatment with VEGF and HS-enhancing agents.
  • Assessed MB231 adhesion and transmigration across the BBB post-treatment.

Main Results:

  • Reduced BBB HS and enhanced MB231 HS increased MB231 adhesion and transmigration.
  • Conversely, enhanced BBB HS and reduced MB231 HS decreased these processes.

Conclusions:

  • VEGF's differential regulation of HS on endothelial cells and breast cancer cells influences brain metastasis.
  • Targeting HS presents a potential therapeutic strategy for inhibiting breast cancer brain metastasis.