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The Glioblastoma Perivascular Microenvironment


Glioblastoma (GBM) is the most fatal and aggressive brain tumor in adults, and with an average prognosis of 15 months, new therapeutic avenues are desperately needed. A major contributing factor to GBM malignancy is the maintenance of a GBM stem cell (GBMSC) population within a tumor propagating perivascular microenvironment, though the specific interactions mediating vascular support of GBMSCs are not well understood. We thus developed a comprehensive interactome, outlining all putative vascular endothelial cell (ECs) ligand-GBMSC receptor interactions as identified through whole transcriptome profiling of ECs and GBMSCs isolated from the same freshly resected primary patient GBM samples. We revealed a prominent role for the perivascular niche (PVN) interactions to be in promoting tumor cell migration and invasion. From our interactome, the function of the EC-secreted Integrin Binding Sialoprotein (IBSP) angiocrine in promoting Proneural GBMSC migration, proliferation, and a transition to a more aggressive Mesenchymal phenotype was specifically demonstrated. Our analyses are a first to report on such a detailed interrogation of the mechanisms of GBMSC dependence on the PVN, and provide a large database to fuel further research in this area.

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