Ontology highlight
ABSTRACT: Background
Glioblastoma (GBM) is one of the most lethal tumor types. Hypercellular regions, named pseudopalisades, are characteristic in these tumors and have been hypothesized to be waves of migrating glioblastoma cells. These "waves" of cells are thought to be induced by oxygen and nutrient depletion caused by tumor-induced blood vessel occlusion. Although the universal presence of these structures in GBM tumors suggests that they may play an instrumental role in GBM's spread and invasion, the recreation of these structures in vitro has remained challenging.Methods
Here we present a new microfluidic model of GBM that mimics the dynamics of pseudopalisade formation. To do this, we embedded U-251 MG cells within a collagen hydrogel in a custom-designed microfluidic device. By controlling the medium flow through lateral microchannels, we can mimic and control blood-vessel obstruction events associated with this disease.Results
Through the use of this new system, we show that nutrient and oxygen starvation triggers a strong migratory process leading to pseudopalisade generation in vitro. These results validate the hypothesis of pseudopalisade formation and show an excellent agreement with a systems-biology model based on a hypoxia-driven phenomenon.Conclusions
This paper shows the potential of microfluidic devices as advanced artificial systems capable of modeling in vivo nutrient and oxygen gradients during tumor evolution.
SUBMITTER: Ayuso JM
PROVIDER: S-EPMC5464359 | biostudies-literature | 2017 Apr
REPOSITORIES: biostudies-literature
Ayuso Jose M JM Monge Rosa R Martínez-González Alicia A Virumbrales-Muñoz María M Llamazares Guillermo A GA Berganzo Javier J Hernández-Laín Aurelio A Santolaria Jorge J Doblaré Manuel M Hubert Christopher C Rich Jeremy N JN Sánchez-Gómez Pilar P Pérez-García Víctor M VM Ochoa Ignacio I Fernández Luis J LJ
Neuro-oncology 20170401 4
<h4>Background</h4>Glioblastoma (GBM) is one of the most lethal tumor types. Hypercellular regions, named pseudopalisades, are characteristic in these tumors and have been hypothesized to be waves of migrating glioblastoma cells. These "waves" of cells are thought to be induced by oxygen and nutrient depletion caused by tumor-induced blood vessel occlusion. Although the universal presence of these structures in GBM tumors suggests that they may play an instrumental role in GBM's spread and invas ...[more]