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Brain cancer stem cells: current status on glioblastoma multiforme.

Facchino S, Abdouh M, Bernier G - Cancers (Basel) (2011)

Bottom Line: GBM tumors are highly heterogeneous.Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cell self-renewal mechanism.GBM tumors are also notorious for their resistance to radiation therapy.

View Article: PubMed Central - PubMed

Affiliation: Developmental Biology Laboratory, Hopital Maisonneuve-Rosemont, 5415 Boul. l'Assomption, Montreal, H1T 2M4, Canada. gbernier.hmr@ssss.gouv.qc.ca.

ABSTRACT
Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cell self-renewal mechanism. GBM tumors are also notorious for their resistance to radiation therapy. Notably, GBM "cancer stem cells" were also found to be responsible for this radioresistance. Herein, we will analyze the data supporting or not the cancer stem cell model in GBM, overview the current knowledge regarding GBM stem cell self-renewal and radioresistance molecular mechanisms, and discuss the potential therapeutic application of these findings.

No MeSH data available.


Related in: MedlinePlus

Scheme illustrating the mammalian neural stem cell niche. The left image represents a coronal view of the adult brain at the level of the lateral ventricule. The subventricular zone (SVZ; brown area) of the cerebral cortex is shown (black box). The enlarged box (right image) describes the architecture of the neural stem cell niche where resident type B cells (blue), C cells (green), A cells (red), and ciliary ependymal cells (peach) are shown. The lateral ventricle (LV) (blue area), the SVZ (brown area) and a blood vessel (BV; red rectangle) are also represented. Based on work from [13,14].
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f1-cancers-03-01777: Scheme illustrating the mammalian neural stem cell niche. The left image represents a coronal view of the adult brain at the level of the lateral ventricule. The subventricular zone (SVZ; brown area) of the cerebral cortex is shown (black box). The enlarged box (right image) describes the architecture of the neural stem cell niche where resident type B cells (blue), C cells (green), A cells (red), and ciliary ependymal cells (peach) are shown. The lateral ventricle (LV) (blue area), the SVZ (brown area) and a blood vessel (BV; red rectangle) are also represented. Based on work from [13,14].

Mentions: In the central nervous system, different NSCs and neural progenitor populations are found starting from early embryogenesis to adult stage. During embryonic brain development, neuroepithelial (NE) progenitors represent the most primitive NSCs. NE progenitors give rise to the first neurons and to basal progenitors (BPs). NE progenitors also produce an intermediate NSC population, the radial glia (RG) [4]. NE progenitors and RG cells can be distinguished by their morphology and expression of specific markers (Table 1). During fetal life, RG cells represent the principal cell type found in developing brain and serve as NSCs and support cells for migrating neurons [4-6]. RG cells display a more restricted differentiation potential compared to NE progenitors [6]. Like NE progenitors, RG cells give rise to BP cells, which primarily reside in the developing telencephalon. BP cells only produce neurons and represent the main neurogenic population during brain development [7-10]. NSCs persist after birth and are responsible for the maintenance of neurogenesis and gliogenesis in the developing and adult brain. Adult NSCs arise from the post-natal differentiation of RG cells [11,12]. Adult NSCs are found in precise regions of the brain, i.e., the SVZ of the cerebral cortex and the subgranular zone (SGZ) of the dentate gyrus. NSCs reside in a specific microenvironment called the stem cell niche. At the ventricular surface, the niche displays a unique pinwheel structure composed of ependymal cells surrounding NSCs, and where NSCs retain a long basal process with blood vessels and a minute apical process with the ventricle [13] (Figure 1). This organization is presumably important for stem cells maintenance, neurogenic activity, and response to environmental cues. In the mouse SVZ, the stem cell niche contains at least four different cell populations: type A cells (neuroblasts), type B cells (quiescent NSCs), type C cells (transit-amplifying cells), and ependymal cells [14]. Type B cells express GFAP and hence are sometimes referred to as stem cell astrocytes (Table 1). Type B cells are responsible for the generation of type C cells, which have a high proliferation potential. Type C cells ultimately differentiate into neuroblasts that migrate to the olfactory bulb and generate interneurons [15-18]. A distinct and possibly more quiescent NSC population of ependymal cells may also exist in the mouse SVZ. These cells do not express GFAP but instead express the cell surface marker CD133/prominin-1 (Table 1). Like type B cells, CD133+/CD24- ependymal cells are able to self-renew and generate neurons, astrocytes, and oligodendrocytes [19]. The second source of neurogenesis in the adult brain is the SGZ. Radial astrocytes or type 1 progenitors within the SGZ represent the primary neuronal precursors. However, radial astrocytes do not directly produce neurons but instead produce an intermediate neurogenic cell population, the type D cell [20,21].


Brain cancer stem cells: current status on glioblastoma multiforme.

Facchino S, Abdouh M, Bernier G - Cancers (Basel) (2011)

Scheme illustrating the mammalian neural stem cell niche. The left image represents a coronal view of the adult brain at the level of the lateral ventricule. The subventricular zone (SVZ; brown area) of the cerebral cortex is shown (black box). The enlarged box (right image) describes the architecture of the neural stem cell niche where resident type B cells (blue), C cells (green), A cells (red), and ciliary ependymal cells (peach) are shown. The lateral ventricle (LV) (blue area), the SVZ (brown area) and a blood vessel (BV; red rectangle) are also represented. Based on work from [13,14].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3757390&req=5

f1-cancers-03-01777: Scheme illustrating the mammalian neural stem cell niche. The left image represents a coronal view of the adult brain at the level of the lateral ventricule. The subventricular zone (SVZ; brown area) of the cerebral cortex is shown (black box). The enlarged box (right image) describes the architecture of the neural stem cell niche where resident type B cells (blue), C cells (green), A cells (red), and ciliary ependymal cells (peach) are shown. The lateral ventricle (LV) (blue area), the SVZ (brown area) and a blood vessel (BV; red rectangle) are also represented. Based on work from [13,14].
Mentions: In the central nervous system, different NSCs and neural progenitor populations are found starting from early embryogenesis to adult stage. During embryonic brain development, neuroepithelial (NE) progenitors represent the most primitive NSCs. NE progenitors give rise to the first neurons and to basal progenitors (BPs). NE progenitors also produce an intermediate NSC population, the radial glia (RG) [4]. NE progenitors and RG cells can be distinguished by their morphology and expression of specific markers (Table 1). During fetal life, RG cells represent the principal cell type found in developing brain and serve as NSCs and support cells for migrating neurons [4-6]. RG cells display a more restricted differentiation potential compared to NE progenitors [6]. Like NE progenitors, RG cells give rise to BP cells, which primarily reside in the developing telencephalon. BP cells only produce neurons and represent the main neurogenic population during brain development [7-10]. NSCs persist after birth and are responsible for the maintenance of neurogenesis and gliogenesis in the developing and adult brain. Adult NSCs arise from the post-natal differentiation of RG cells [11,12]. Adult NSCs are found in precise regions of the brain, i.e., the SVZ of the cerebral cortex and the subgranular zone (SGZ) of the dentate gyrus. NSCs reside in a specific microenvironment called the stem cell niche. At the ventricular surface, the niche displays a unique pinwheel structure composed of ependymal cells surrounding NSCs, and where NSCs retain a long basal process with blood vessels and a minute apical process with the ventricle [13] (Figure 1). This organization is presumably important for stem cells maintenance, neurogenic activity, and response to environmental cues. In the mouse SVZ, the stem cell niche contains at least four different cell populations: type A cells (neuroblasts), type B cells (quiescent NSCs), type C cells (transit-amplifying cells), and ependymal cells [14]. Type B cells express GFAP and hence are sometimes referred to as stem cell astrocytes (Table 1). Type B cells are responsible for the generation of type C cells, which have a high proliferation potential. Type C cells ultimately differentiate into neuroblasts that migrate to the olfactory bulb and generate interneurons [15-18]. A distinct and possibly more quiescent NSC population of ependymal cells may also exist in the mouse SVZ. These cells do not express GFAP but instead express the cell surface marker CD133/prominin-1 (Table 1). Like type B cells, CD133+/CD24- ependymal cells are able to self-renew and generate neurons, astrocytes, and oligodendrocytes [19]. The second source of neurogenesis in the adult brain is the SGZ. Radial astrocytes or type 1 progenitors within the SGZ represent the primary neuronal precursors. However, radial astrocytes do not directly produce neurons but instead produce an intermediate neurogenic cell population, the type D cell [20,21].

Bottom Line: GBM tumors are highly heterogeneous.Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cell self-renewal mechanism.GBM tumors are also notorious for their resistance to radiation therapy.

View Article: PubMed Central - PubMed

Affiliation: Developmental Biology Laboratory, Hopital Maisonneuve-Rosemont, 5415 Boul. l'Assomption, Montreal, H1T 2M4, Canada. gbernier.hmr@ssss.gouv.qc.ca.

ABSTRACT
Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cell self-renewal mechanism. GBM tumors are also notorious for their resistance to radiation therapy. Notably, GBM "cancer stem cells" were also found to be responsible for this radioresistance. Herein, we will analyze the data supporting or not the cancer stem cell model in GBM, overview the current knowledge regarding GBM stem cell self-renewal and radioresistance molecular mechanisms, and discuss the potential therapeutic application of these findings.

No MeSH data available.


Related in: MedlinePlus