A novel 3D nanofibre scaffold conserves the plasticity of glioblastoma stem cell invasion by regulating galectin-3 and integrin-β1 expression

Scientific Reports volume 9, Article number: 14612 (2019) 

Ali Saleh1, Emilie Marhuenda1, Christine Fabre1, Zahra Hassani1, Jan De Weille1, Hassan Boukhaddaoui1, Sophie Guelfi1, Igor Lima Maldonado2, Jean- Philippe Hugnot1, Hugues Duffau1, Luc Bauchet1, David Cornu3, Norbert Bakalara1,

1 INM - Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs
2 Univ Tours, CHRU Tours, Le Studium Loire Valley Inst Adv Studies, INSERM,Tours,Ibrain,UMR 1253, Tours, France
3 IEM - Institut Européen des membranes


Glioblastoma Multiforme (GBM) invasiveness renders complete surgical resection impossible and highly invasive Glioblastoma Initiating Cells (GICs) are responsible for tumour recurrence. Their dissemination occurs along pre-existing fibrillary brain structures comprising the aligned myelinated fibres of the corpus callosum (CC) and the laminin (LN)-rich basal lamina of blood vessels. The extracellular matrix (ECM) of these environments regulates GIC migration, but the underlying mechanisms remain largely unknown. In order to recapitulate the composition and the topographic properties of the cerebral ECM in the migration of GICs, we have set up a new aligned polyacrylonitrile (PAN)-derived nanofiber (NF) scaffold. This system is suitable for drug screening as well as discrimination of the migration potential of different glioblastoma stem cells. Functionalisation with LN increases the spatial anisotropy of migration and modulates its mode from collective to single cell migration. Mechanistically, equally similar to what has been observed for mesenchyma I migration of GBM in vivo, is the upregulation of galectin-3 and integrin-beta 1 in Gli4 cells migrating on our NF scaffold. Downregulation of Calpain-2 in GICs migrating in vivo along the CC and in vitro on LN-coated NF underlines a difference in the turnover of focal adhesion (FA) molecules between single-cell and collective types of migration.


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