Abstract
As most common primary brain cancer, glioblastoma is also the most aggressive and malignant form of cancer in the adult central nervous system. Glioblastomas are genetic and transcriptional heterogeneous tumors, which in spite of intensive research are poorly understood. Over the years conventional therapies failed to affect a cure, resulting in low survival rates of affected patients. To improve the clinical outcome, an important approach is to identify the cells of origin. One potential source for these are neural stem cells (NSCs) located in the subventricular zone, which is one of two niches in the adult nervous system where NSCs with the capacity of self-renewal and proliferation reside. These cells normally give rise to neuronal as well as glial progenitor cells. This review summarizes current findings about links between NSCs and cancer stem cells in glioblastoma and discusses current therapeutic approaches, which arise as a result of identifying the cell of origin in glioblastoma.
Highlights
Glioblastoma (GB) is the most frequent form of brain tumor in adults and is associated with a poor prognosis and a short median patient survival [1]
A limited number of cells in the tumor displayed tumorigenic potential which they identified by cell surface markers (CD44+ CD24−/low lineage− ) [94]. Targeting these cells by cancer therapy would be most promising. In addition to their tumorigenic properties and extensive proliferative potential, cancer stem cells (CSCs) share various qualities with normal stem cells: (I) The capacity of multipotency, meaning the ability to differentiate into multiple lineages, self-renewal, and the capacity to divide into either new stem cells or into differentiated cells [86]. (II) A low self-renewal rate and rare occurrence [92,93,95,96]. (III) A strict control by their microenvironment to regulate the balance between proliferation and cell death [97,98]. (IV) The usage of similar signaling pathways [85]
Over the years of glioblastoma research, various theories emerged about the cell of origin, including tissue-specific stem cells like neural stem cells (NSCs) or committed precursor cells, like astrocyte precursor cells (APCs) and oligodendrocyte precursor cells (OPCs) [119,120]
Summary
Glioblastoma (GB) is the most frequent form of brain tumor in adults and is associated with a poor prognosis and a short median patient survival [1]. Limited therapeutic options, combined with a poor response to currently used therapies, increased the pressure to discover new genetic, epigenetic and molecular pathways involved in GB to create new therapies. The existence of brain tumor propagating cells (BTPCs) and their molecular, genetic, and epigenetic footprint could open new ways of therapeutic approaches. Diverse tumors could be retraced to mutations in stem cells [4] and various studies have suggested that NSCs might be the cells of origin of GB, including mutated astrocyte-like NSCs from the SVZ [5,6,7,8]. Recent studies reported from clinics and mouse models that glioblastoma arise from migration of mutated astrocyte-like NSCs from the SVZ [8]
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