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March 6th, 2025
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ETH Zurich
bioengineering
biorxiv

Real-Time Tracking of Tumor Invasion Dynamics in Organotypic Brain Slices at Subcellular Resolution

Petr, J. B.Open in Google Scholar•Lin, M.-S.Open in Google Scholar•Hochuli, D.Open in Google Scholar•Hierlemann, A.Open in Google Scholar•Baumgartner, M. B.Open in Google Scholar•Modena, M. M.Open in Google Scholar

Understanding how tumor cells invade and interact with their microenvironment is crucial for advancing cancer treatment strategies. However, replicating in vitro the heterogeneity and cytoarchitecture of organs, particularly of the brain, remains highly challenging. Here, we developed a tumor / brain slice co-culture model to investigate how medulloblastoma cancer cells invade the cerebellar microenvironment. To monitor invasion in real time, we devised PHIROS, a microfluidic Platform for High-Resolution Imaging of Organotypic Slices. PHIROS enables the aseptic culturing of organotypic slices and long-term, high-resolution imaging of invading tumor cells in cerebellar slices. Tissue health could be maintained over multiple days by controlled perfusion with oxygenated medium in a closed environment, and tissue functionality was confirmed through spontaneous astrocytic calcium signals during perfusion culturing. We utilized PHIROS to observe actin cytoskeleton reorganization and the dynamic localization of the immune-checkpoint marker B7-H3 during cancer invasion, and to see how cancer cells responded to and remodeled their microenvironment. PHIROS provided novel insights into medulloblastoma cell invasion in a physiologically relevant model with the potential to unlock new therapeutic strategies.

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