Neural Stem Cells as Potential Glioblastoma Cells of Origin

Abstract

Glioblastoma multiforme (GBM) is the most malignant brain tumor in adults and it remains incurable. These tumors are very heterogeneous, resistant to cytotoxic therapies, and they show high rates of invasiveness. Therefore, patients face poor prognosis, and the survival rates remain very low. Previous research states that GBM contains a cell population with stem cell characteristics called glioma stem cells (GSCs). These cells are able to self-renew and regenerate the tumor and, therefore, they are partly responsible for the observed resistance to therapies and tumor recurrence. Recent data indicate that neural stem cells (NSCs) in the subventricular zone (SVZ) are the cells of origin of GBM, that is, the cell type acquiring the initial tumorigenic mutation. The involvement of SVZ-NSCs is also associated with GBM progression and recurrence. Identifying the cellular origin of GBM is important for the development of early detection techniques and the discovery of early disease markers. In this review, we analyze the SVZ-NSC population as a potential GBM cell of origin, and its potential role for GBM therapies.

Targeting CDK4/6 in glioblastoma via in situ injection of a cellulose-based hydrogel

“…Glioma stem cells (GSCs) constitute a self-renewing and slow-dividing sub-population within GBM. 25,26 They recapitulate the heterogeneity of their parent glioma tissues and show similarity in drug resistance and refraction to treatment to clinical GBM cases. As shown in Fig.…”

MAPP unravels frequent co-regulation of splicing and polyadenylation by RNA-binding proteins and their dysregulation in cancer

“…Thus, the high expression of PTBP1 in glioblastomas relative to normal brain tissue might contribute to a less differentiated state, which was suggested to be the origin of glioblastoma 42 , and is also one of the general hallmarks of cancer 43 . The cell type at the origin of GBM that acquires the initial oncogenic mutations is still unknown, although recent research suggests that this cell type might be NSCs, which reside in the ventricles of the brain during development 44 . To investigate this further from a splicing perspective, we used MAPP, comparing cells from the ventricular zone (VZ) to cells from the cortical plate (CP) 45 .…”

Gene Expression of GABAA Receptor Subunits and Association with Patient Survival in Glioma

“…These cells can contain many of the driver mutations that give rise to GBM, share molecular features with GBM cells, and display migratory patterns from the SVZ to the tumor. In addition, key genetic mutations in GBM are associated with genes that regulate neuronal function in the SVZ [ 8 , 9 , 10 , 11 , 12 ].…”

“…In addition to mediating fast neuronal inhibition in the adult brain, GABA and its receptors regulate CNS development [ 19 ], proliferation and differentiation of neural stem cells and neuronal progenitors [ 20 , 21 , 22 ], and adult neurogenesis [ 20 , 23 , 24 , 25 ]. As discussed above, neural stem cells in the SVZ are proposed as cells of origin in GBM [ 8 , 9 , 10 , 11 , 12 ]. GABA has been shown to depolarize neuronal progenitors in the SVZ through activation of GABA A receptors [ 26 ].…”