4.6 Article

Comparative dynamics of microglial and glioma cell motility at the infiltrative margin of brain tumours

Journal

JOURNAL OF THE ROYAL SOCIETY INTERFACE
Volume 15, Issue 139, Pages -

Publisher

ROYAL SOC
DOI: 10.1098/rsif.2017.0582

Keywords

time lapse microscopy; PDGF rat model; anomalous diffusion; particle image velocimetry; glioblastoma

Funding

  1. James S. McDonnell Foundation
  2. Ivy Foundation
  3. Mayo Clinic
  4. NIH [R01 NS060752, R01 CA164371, U54 CA210180, U54 CA143970, U54 CA193489]

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Microglia are a major cellular component of gliomas, and abundant in the centre of the tumour and at the infiltrative margins. While glioma is a notoriously infiltrative disease, the dynamics of microglia and glioma migratory patterns have not been well characterized. To investigate the migratory behaviour of microglia and glioma cells at the infiltrative edge, we performed two-colour time-lapse fluorescence microscopy of brain slices generated from a platelet-derived growth factor-B (PDGFB)-driven rat model of glioma, in which glioma cells and microglia were each labelled with one of two different fluorescent markers. We used mathematical techniques to analyse glioma cells and microgliamotility with both single cell tracking and particle image velocimetry (PIV). Our results show microglia motility is strongly correlated with the presence of glioma, while the correlation of the speeds of glioma cells and microglia was variable and weak. Additionally, we showed that microglia and glioma cells exhibit different types of diffusive migratory behaviour. Microglia movement fit a simple random walk, while glioma cell movement fits a super diffusion pattern. These results show that glioma cells stimulate microglia motility at the infiltrative margins, creating a correlation between the spatial distribution of glioma cells and the pattern of microglia motility.

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