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Malignant gliomas are devastating, aggressive tumours that frequently kill patients with a low survival rate (1 year after diagnosis). Diffuse invasion of glioma cells after surgical resection in brain tissue is a major obstacle for effective therapy. Glioma cells use the tortuous extracellular routes of migration, using blood vessels as guides. These cells manipulate ion channels in the local microenvironment to dynamically adjust their cell volume to accommodate to narrow spaces and breach the blood-brain barrier through disruption of astrocytic endfeet, that support blood vessels. We investigated the cell-mechanical aspect of glioma cell migration along the blood vessels by using an immersed boundary method without volume convervation. This involves many intercellular interactions and biochemical reactions. We illustrate that the viscoelastic properties of the glioma cell and ion-induced reduction in volume enable them to penetrate the narrow gap. The unique biology of glioma invasion provides unexplored brain-specific therapeutic targets for this devastating disease with little effective treatment options.
[1] V.A. Cuddapah, S. Robel, S. Watkins, and H. Sontheimer. A neuro-centric perspective on glioma invasion. Nature Reviews Neuroscience, 15(7):455-465, 2014
