Glioblastoma on a microfluidic chip: Generating pseudopalisades and enhancing cancer cell’s aggressiveness through blood vessel obstruction events
2016 - JM Ayuso, R Monge, A Martínez-González, GA Llamazares, J Berganzo, A Hernández-Laín, J Santolaria, M Doblaré, C Hubert, J Rich, P Sánchez-Gómez, VM Pérez-García, I Ochoa, LJ Fernández
Neuro-Oncology (2016) doi:10.1093/neuonc/now230
Resumen
Glioblastoma is one of the most infiltrating tumors. Characteristic hypercellular regions, named pseudopalisades, are observed in these tumors that have been explained as waves of migrating glioblastoma cells. These “waves” of cells are induced by oxygen and nutrient depletion caused by tumor-induced blood vessel occlusion. These structures seem to play an instrumental role on GBM spreading and invasion, however the recreation of these structures "in vitro" remains challenging. We present a new microfluidic model that mimics the dynamics of pseudopalisade formation. U-251 Cells have been embedded within a collagen hydrogel in a microfluidic device. Controlling the medium flow through the lateral microchannels we mimic the thrombotic event associated to this disease. Nutrient and oxygen starvation triggers a strong migratory process leading to pseudopalisade generation. The results validate the hypothesis of pseudopalisade formation, with an excellent agreement with a systems-biology model based on hypoxia-driven phenomenon. This interdisciplinary approach provides an example of the use of these microfluidic devices as advanced artificial systems with spatial gradients on nutrients that allow the validation of biological hypothesis.