Abstract
Human glioblastoma is the most aggressive type of primary malignant brain tumors. Standard treatment includes surgical resection followed by radiation and chemotherapy but it only provides short-term benefits and the prognosis of these brain tumors is still very poor. Glioblastomas contain a population of glioma stem cells (GSCs), with self-renewal ability, which are partly responsible for the tumor resistance to therapy and for the tumor recurrence after treatment. The human adult subventricular zone contains astrocyte-like neural stem cells (NSCs) that are probably reminiscent of the radial glia present in embryonic brain development. There are numerous molecules involved in the biology of subventricular zone NSCs that are also instrumental in glioblastoma development. These include cytoskeletal proteins, telomerase, tumor suppressor proteins, transcription factors, and growth factors. Interestingly, genes encoding these molecules are frequently mutated in glioblastoma cells. Indeed, it has been recently shown that NSCs in the subventricular zone are a potential cell of origin that contains the driver mutations of human glioblastoma. In this review we will describe common features between GSCs and subventricular zone NSCs, and we will discuss the relevance of this important finding in terms of possible future therapeutic strategies.
Highlights
Glioblastoma (GBM) is the most malignant primary brain tumor in humans
What remains unsolved is which is the homolog to these type C highly EGFresponsive cells in the human subventricular zone (SVZ). These results suggest that mutations in the epidermal growth factor receptor (EGFR) leading to activated EGFR signaling, in more quiescent or in more proliferative neural stem cells (NSCs) of the human SVZ, may result in the migration of SVZ cells into the parenchyma and subsequent generation of gliomas or other brain tumors
All the results demonstrate that NSCs in human SVZ tissue are the cells of origin that contain the driver mutations, at least in IDH1 wild-type GBM
Summary
Glioblastoma (GBM) is the most malignant primary brain tumor in humans. The World Health Organization classified this tumor as Grade IV glioblastoma, and consists of poorly differentiated cells with vascular proliferation and pseudopalisading necrosis. These results suggest that mutations in the EGFR leading to activated EGFR signaling, in more quiescent or in more proliferative NSCs of the human SVZ, may result in the migration of SVZ cells into the parenchyma and subsequent generation of gliomas or other brain tumors.
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