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Brain tumor stem cells as therapeutic targets in models of glioma.

Laks DR, Visnyei K, Kornblum HI - Yonsei Med. J. (2010)

Bottom Line: At this time, brain tumor stem cells remain a controversial hypothesis while malignant brain tumors continue to present a dire prognosis of severe morbidity and mortality.However, due to the multiple oncogenic pathways involved in glioma, it is necessary to determine which pathways are the essential targets for therapy.Furthermore, research still needs to comprehend the morphogenic processes of cell populations involved in tumor formation.

View Article: PubMed Central - PubMed

Affiliation: Intellectual and Developmental Disability Research Center, UCLA Medical Center, Los Angeles, California, USA.

ABSTRACT
At this time, brain tumor stem cells remain a controversial hypothesis while malignant brain tumors continue to present a dire prognosis of severe morbidity and mortality. Yet, brain tumor stem cells may represent an essential cellular target for glioma therapy as they are postulated to be the tumorigenic cells responsible for recurrence. Targeting oncogenic pathways that are essential to the survival and growth of brain tumor stem cells represents a promising area for developing therapeutics. However, due to the multiple oncogenic pathways involved in glioma, it is necessary to determine which pathways are the essential targets for therapy. Furthermore, research still needs to comprehend the morphogenic processes of cell populations involved in tumor formation. Here, we review research and discuss perspectives on models of glioma in order to delineate the current issues in defining brain tumor stem cells as therapeutic targets in models of glioma.

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Related in: MedlinePlus

Different tumor models of GBM. According to the cancer stem cell model (left panel), a subpopulation of cancer cells possesses the capacity of self-renewal, clonal sphere formation and in vivo tumor formation, as well as the capability to form progeny with a more restricted fate (darker colors). This forms a hierarchical lineage system where the primary therapeutic cell target is the CSC itself. The clonal evolution model (middle panel) exhibits no lineage hierarchy, as the multiple cell populations are the result of different genetic mutations (broken arrows). There is no cell hierarchy, because most of these cell subtypes self-renew and are capable of tumor formation, which makes them all targets of therapeutic interventions. In a complex system (right panel), both genetic and epigenetic changes might occur within a single tumor, resulting in a multifaceted cell system where several tumor-initiating cell types may coexist. While genetic mutations may produce new tumor cell populations (#3), epigenetic changes (#2) might enable cells to produce progeny with a more or less restricted fate and also to temporarily adopt different states characterized by therapy resistance and expression of different cell markers. Another important feature of a complex system is that the individual cell populations interact (red arrows, #4). While all potential tumor forming cells have to be targeted for successful therapy in this model, the interruption of the cell-cell and cell-niche interactions may also weaken the tumor system as a whole. GBM, glioblastoma multiforme; CSC, cancer stem cell.
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Figure 1: Different tumor models of GBM. According to the cancer stem cell model (left panel), a subpopulation of cancer cells possesses the capacity of self-renewal, clonal sphere formation and in vivo tumor formation, as well as the capability to form progeny with a more restricted fate (darker colors). This forms a hierarchical lineage system where the primary therapeutic cell target is the CSC itself. The clonal evolution model (middle panel) exhibits no lineage hierarchy, as the multiple cell populations are the result of different genetic mutations (broken arrows). There is no cell hierarchy, because most of these cell subtypes self-renew and are capable of tumor formation, which makes them all targets of therapeutic interventions. In a complex system (right panel), both genetic and epigenetic changes might occur within a single tumor, resulting in a multifaceted cell system where several tumor-initiating cell types may coexist. While genetic mutations may produce new tumor cell populations (#3), epigenetic changes (#2) might enable cells to produce progeny with a more or less restricted fate and also to temporarily adopt different states characterized by therapy resistance and expression of different cell markers. Another important feature of a complex system is that the individual cell populations interact (red arrows, #4). While all potential tumor forming cells have to be targeted for successful therapy in this model, the interruption of the cell-cell and cell-niche interactions may also weaken the tumor system as a whole. GBM, glioblastoma multiforme; CSC, cancer stem cell.

Mentions: In order to model the tumorigenic process of glioma, it is necessary to ascertain which processes are involved. Besides the brain tumor stem cell model and the clonal evolution model are more complex systems whose roles in glioma are in the realm of possibility (Fig. 1). In order to prioritize therapeutic targets of glioma, it is important to have the most informative model of glioma tumorigenesis. Further research is needed to determine whether de-differentiation occurs, whether BTSC can adapt to treatment by switching between different phenotypic states that confer either resistance or growth, whether multiple, genetically distinct brain tumor stem cells exist within each tumor, whether a mixture of the clonal model and the BTSC model co-exist, and to what extent signaling between BTSC, tumor cells, and the niche provides additional therapeutic targets.


Brain tumor stem cells as therapeutic targets in models of glioma.

Laks DR, Visnyei K, Kornblum HI - Yonsei Med. J. (2010)

Different tumor models of GBM. According to the cancer stem cell model (left panel), a subpopulation of cancer cells possesses the capacity of self-renewal, clonal sphere formation and in vivo tumor formation, as well as the capability to form progeny with a more restricted fate (darker colors). This forms a hierarchical lineage system where the primary therapeutic cell target is the CSC itself. The clonal evolution model (middle panel) exhibits no lineage hierarchy, as the multiple cell populations are the result of different genetic mutations (broken arrows). There is no cell hierarchy, because most of these cell subtypes self-renew and are capable of tumor formation, which makes them all targets of therapeutic interventions. In a complex system (right panel), both genetic and epigenetic changes might occur within a single tumor, resulting in a multifaceted cell system where several tumor-initiating cell types may coexist. While genetic mutations may produce new tumor cell populations (#3), epigenetic changes (#2) might enable cells to produce progeny with a more or less restricted fate and also to temporarily adopt different states characterized by therapy resistance and expression of different cell markers. Another important feature of a complex system is that the individual cell populations interact (red arrows, #4). While all potential tumor forming cells have to be targeted for successful therapy in this model, the interruption of the cell-cell and cell-niche interactions may also weaken the tumor system as a whole. GBM, glioblastoma multiforme; CSC, cancer stem cell.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2908869&req=5

Figure 1: Different tumor models of GBM. According to the cancer stem cell model (left panel), a subpopulation of cancer cells possesses the capacity of self-renewal, clonal sphere formation and in vivo tumor formation, as well as the capability to form progeny with a more restricted fate (darker colors). This forms a hierarchical lineage system where the primary therapeutic cell target is the CSC itself. The clonal evolution model (middle panel) exhibits no lineage hierarchy, as the multiple cell populations are the result of different genetic mutations (broken arrows). There is no cell hierarchy, because most of these cell subtypes self-renew and are capable of tumor formation, which makes them all targets of therapeutic interventions. In a complex system (right panel), both genetic and epigenetic changes might occur within a single tumor, resulting in a multifaceted cell system where several tumor-initiating cell types may coexist. While genetic mutations may produce new tumor cell populations (#3), epigenetic changes (#2) might enable cells to produce progeny with a more or less restricted fate and also to temporarily adopt different states characterized by therapy resistance and expression of different cell markers. Another important feature of a complex system is that the individual cell populations interact (red arrows, #4). While all potential tumor forming cells have to be targeted for successful therapy in this model, the interruption of the cell-cell and cell-niche interactions may also weaken the tumor system as a whole. GBM, glioblastoma multiforme; CSC, cancer stem cell.
Mentions: In order to model the tumorigenic process of glioma, it is necessary to ascertain which processes are involved. Besides the brain tumor stem cell model and the clonal evolution model are more complex systems whose roles in glioma are in the realm of possibility (Fig. 1). In order to prioritize therapeutic targets of glioma, it is important to have the most informative model of glioma tumorigenesis. Further research is needed to determine whether de-differentiation occurs, whether BTSC can adapt to treatment by switching between different phenotypic states that confer either resistance or growth, whether multiple, genetically distinct brain tumor stem cells exist within each tumor, whether a mixture of the clonal model and the BTSC model co-exist, and to what extent signaling between BTSC, tumor cells, and the niche provides additional therapeutic targets.

Bottom Line: At this time, brain tumor stem cells remain a controversial hypothesis while malignant brain tumors continue to present a dire prognosis of severe morbidity and mortality.However, due to the multiple oncogenic pathways involved in glioma, it is necessary to determine which pathways are the essential targets for therapy.Furthermore, research still needs to comprehend the morphogenic processes of cell populations involved in tumor formation.

View Article: PubMed Central - PubMed

Affiliation: Intellectual and Developmental Disability Research Center, UCLA Medical Center, Los Angeles, California, USA.

ABSTRACT
At this time, brain tumor stem cells remain a controversial hypothesis while malignant brain tumors continue to present a dire prognosis of severe morbidity and mortality. Yet, brain tumor stem cells may represent an essential cellular target for glioma therapy as they are postulated to be the tumorigenic cells responsible for recurrence. Targeting oncogenic pathways that are essential to the survival and growth of brain tumor stem cells represents a promising area for developing therapeutics. However, due to the multiple oncogenic pathways involved in glioma, it is necessary to determine which pathways are the essential targets for therapy. Furthermore, research still needs to comprehend the morphogenic processes of cell populations involved in tumor formation. Here, we review research and discuss perspectives on models of glioma in order to delineate the current issues in defining brain tumor stem cells as therapeutic targets in models of glioma.

Show MeSH
Related in: MedlinePlus