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Glioma Cell Migration Dynamics in Brain Tissue Assessed by Multimodal Optical Imaging.

Chao J Liu1, Ghaidan A Shamsan1, Taner Akkin1

  • 1Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota.

Biophysical Journal
|September 3, 2019
PubMed
Summary

Glioblastoma cells surprisingly migrate along blood vessels, not white matter tracts, in the brain. Effective anti-invasion strategies must target both perivascular and blood vessel-associated invasion routes.

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Area of Science:

  • Neuro-oncology
  • Cellular Biology
  • Biophysics

Background:

  • Glioblastoma invasion follows white matter tracts and vasculature.
  • Understanding glioma cell migration routes is crucial for developing anti-invasive therapies.

Purpose of the Study:

  • To systematically quantify the migration routes and motility of U251 human glioblastoma cells in mouse brain slices.
  • To investigate the preferred invasion pathways and migration dynamics of glioma cells in different brain regions.

Main Methods:

  • Multimodal imaging combining polarization-sensitive optical coherence tomography (PS-OCT) and confocal fluorescence microscopy.
  • PS-OCT for delineating nerve fiber tracts.
  • Confocal microscopy for imaging cell migration and brain vasculature.

Main Results:

  • U251 glioma cells preferentially migrate along vasculature in both gray and white matter, contrary to expectations.
  • Cell motility was significantly higher in gray matter (91 μm²/h) compared to white matter (43 μm²/h).
  • U251 cells exert traction forces on the vasculature, suggesting a "motor-clutch" migration model.

Conclusions:

  • Glioma cell invasion is not solely dependent on white matter tracts.
  • Vasculature serves as a primary route for glioblastoma invasion in both gray and white matter.
  • Anti-invasive strategies should target both perivascular and televascular invasion pathways.