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Glioblastoma-initiating cells: relationship with neural stem cells and the micro-environment.

Goffart N, Kroonen J, Rogister B - Cancers (Basel) (2013)

Bottom Line: However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes.On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal.In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liège, Liège 4000, Belgium. Bernard.Register@ulg.ac.be.

ABSTRACT
Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This "seed-and-soil" relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their "stem cell" properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology.

No MeSH data available.


Related in: MedlinePlus

Relationship between the adult neurogenic niches and glioblastoma-initiating cells. GICs (light purple) have been found to play an important role in GBM aggressiveness and the resistance of the tumor to current treatments, making them an attractive target for therapeutic interventions. However, the design of new GIC inhibitors has proven difficult because their definition is nowadays still confused by the twilight zone of their origin. Indeed, whether GICs are derived from NPCs (yellow) or differentiated/mature cells remains uncertain. In any case, the vascular niche offered by the brain SVZ might be of interest to maintain GICs’ features, even if they are not indigenous. Undoubtedly, particular characteristics of this specific niche and its localization away from the tumor mass make it a significant resource for tumor recurrence. It is expected that future therapies targeting GBM, GICs and their specific environment will help to increase the dramatic survival rate of GBM patients.
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cancers-05-01049-f003: Relationship between the adult neurogenic niches and glioblastoma-initiating cells. GICs (light purple) have been found to play an important role in GBM aggressiveness and the resistance of the tumor to current treatments, making them an attractive target for therapeutic interventions. However, the design of new GIC inhibitors has proven difficult because their definition is nowadays still confused by the twilight zone of their origin. Indeed, whether GICs are derived from NPCs (yellow) or differentiated/mature cells remains uncertain. In any case, the vascular niche offered by the brain SVZ might be of interest to maintain GICs’ features, even if they are not indigenous. Undoubtedly, particular characteristics of this specific niche and its localization away from the tumor mass make it a significant resource for tumor recurrence. It is expected that future therapies targeting GBM, GICs and their specific environment will help to increase the dramatic survival rate of GBM patients.

Mentions: The discovery by Eriksson et al., in 1998, of neural progenitor cells (NPCs) capable of becoming mature neurons in the human brain, thought for decades to be a quiescent organ, has brought the brain’s plasticity into sharp focus [103]. However, researches about stem cells implication in neurological disorder repair have met little success so far and their capacity to regenerate neurons after a lesion is, for now on, very limited. Indeed, NPCs were only found to replace interneurons in specific regions of the brain such as the olfactory bulbs or the dentatus gyrus. Human NPCs, which look like glial cells but with stem cell features, remain in the adult brain in two restricted regions after that the hippocampal sulcus has become the subgranular zone (SGZ) of the hippocampus and the lateral ganglionic eminences turned into the SVZ [104,105]. Because neurogenesis in the SGZ is rigidly fixed by the age of 30 and is composed of a very small number of cells and nor could a link be established between the hippocampus and brain tumors, we will only focus on the SVZ environment in this review. As a matter of fact, the SVZ is the region that borders the ependymal layer on the lateral wall of the lateral ventricle and is separated from the caudate nucleus by a layer of myelin [106]. In the late 90s, specific culture conditions, using neurosphere formation, were used in order to isolate cells from the lateral wall of the temporal lobe in epileptic patients. These experiments already suggested at that time the presence of human NSCs in the adult brain [107,108,109]. As shown in rodent, progenitor cells located in this specific area are able to produce neuroblasts which migrate and integrate the olfactory bulbs. However, it seems that there is a considerably less activity in the human SVZ compared to rodents. Nevertheless, those human progenitors have the ability to proliferate and migrate towards injured regions close to the SVZ. This should be taken into consideration for the development of new treatment in neurological disorders and for our basic understanding of GBM (Figure 3).


Glioblastoma-initiating cells: relationship with neural stem cells and the micro-environment.

Goffart N, Kroonen J, Rogister B - Cancers (Basel) (2013)

Relationship between the adult neurogenic niches and glioblastoma-initiating cells. GICs (light purple) have been found to play an important role in GBM aggressiveness and the resistance of the tumor to current treatments, making them an attractive target for therapeutic interventions. However, the design of new GIC inhibitors has proven difficult because their definition is nowadays still confused by the twilight zone of their origin. Indeed, whether GICs are derived from NPCs (yellow) or differentiated/mature cells remains uncertain. In any case, the vascular niche offered by the brain SVZ might be of interest to maintain GICs’ features, even if they are not indigenous. Undoubtedly, particular characteristics of this specific niche and its localization away from the tumor mass make it a significant resource for tumor recurrence. It is expected that future therapies targeting GBM, GICs and their specific environment will help to increase the dramatic survival rate of GBM patients.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3795378&req=5

cancers-05-01049-f003: Relationship between the adult neurogenic niches and glioblastoma-initiating cells. GICs (light purple) have been found to play an important role in GBM aggressiveness and the resistance of the tumor to current treatments, making them an attractive target for therapeutic interventions. However, the design of new GIC inhibitors has proven difficult because their definition is nowadays still confused by the twilight zone of their origin. Indeed, whether GICs are derived from NPCs (yellow) or differentiated/mature cells remains uncertain. In any case, the vascular niche offered by the brain SVZ might be of interest to maintain GICs’ features, even if they are not indigenous. Undoubtedly, particular characteristics of this specific niche and its localization away from the tumor mass make it a significant resource for tumor recurrence. It is expected that future therapies targeting GBM, GICs and their specific environment will help to increase the dramatic survival rate of GBM patients.
Mentions: The discovery by Eriksson et al., in 1998, of neural progenitor cells (NPCs) capable of becoming mature neurons in the human brain, thought for decades to be a quiescent organ, has brought the brain’s plasticity into sharp focus [103]. However, researches about stem cells implication in neurological disorder repair have met little success so far and their capacity to regenerate neurons after a lesion is, for now on, very limited. Indeed, NPCs were only found to replace interneurons in specific regions of the brain such as the olfactory bulbs or the dentatus gyrus. Human NPCs, which look like glial cells but with stem cell features, remain in the adult brain in two restricted regions after that the hippocampal sulcus has become the subgranular zone (SGZ) of the hippocampus and the lateral ganglionic eminences turned into the SVZ [104,105]. Because neurogenesis in the SGZ is rigidly fixed by the age of 30 and is composed of a very small number of cells and nor could a link be established between the hippocampus and brain tumors, we will only focus on the SVZ environment in this review. As a matter of fact, the SVZ is the region that borders the ependymal layer on the lateral wall of the lateral ventricle and is separated from the caudate nucleus by a layer of myelin [106]. In the late 90s, specific culture conditions, using neurosphere formation, were used in order to isolate cells from the lateral wall of the temporal lobe in epileptic patients. These experiments already suggested at that time the presence of human NSCs in the adult brain [107,108,109]. As shown in rodent, progenitor cells located in this specific area are able to produce neuroblasts which migrate and integrate the olfactory bulbs. However, it seems that there is a considerably less activity in the human SVZ compared to rodents. Nevertheless, those human progenitors have the ability to proliferate and migrate towards injured regions close to the SVZ. This should be taken into consideration for the development of new treatment in neurological disorders and for our basic understanding of GBM (Figure 3).

Bottom Line: However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes.On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal.In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liège, Liège 4000, Belgium. Bernard.Register@ulg.ac.be.

ABSTRACT
Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This "seed-and-soil" relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their "stem cell" properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology.

No MeSH data available.


Related in: MedlinePlus