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Cancer Stem Cells and Pediatric Solid Tumors.

Friedman GK, Gillespie GY - Cancers (Basel) (2011)

Bottom Line: Recently, a subpopulation of cells, termed tumor-initiating cells or tumor stem cells (TSC), has been identified in many different types of solid tumors.Much of the research on TSC has focused on adult cancers.With considerable differences in tumor biology between adult and pediatric cancers, there may be significant differences in the presence, function and behavior of TSC in pediatric malignancies.

View Article: PubMed Central - PubMed

Affiliation: Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.

ABSTRACT
Recently, a subpopulation of cells, termed tumor-initiating cells or tumor stem cells (TSC), has been identified in many different types of solid tumors. These TSC, which are typically more resistant to chemotherapy and radiation compared to other tumor cells, have properties similar to normal stem cells including multipotency and the ability to self-renew, proliferate, and maintain the neoplastic clone. Much of the research on TSC has focused on adult cancers. With considerable differences in tumor biology between adult and pediatric cancers, there may be significant differences in the presence, function and behavior of TSC in pediatric malignancies. We discuss what is currently known about pediatric solid TSC with specific focus on TSC markers, tumor microenvironment, signaling pathways, therapeutic resistance and potential future therapies to target pediatric TSC.

No MeSH data available.


Related in: MedlinePlus

(A) Glioblastoma multiforme cells grown as neurospheres in serum-free medium supplemented with epidermal growth factor and basic fibroblast growth factor. (B) Cells grown in DMEM with fetal bovine serum and L-glutamine.
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f1-cancers-03-00298: (A) Glioblastoma multiforme cells grown as neurospheres in serum-free medium supplemented with epidermal growth factor and basic fibroblast growth factor. (B) Cells grown in DMEM with fetal bovine serum and L-glutamine.

Mentions: The most widely used cell surface molecule relied upon as a TSC marker is CD133 or prominin-1, a transmembrane protein with uncertain biological function that was initially discovered on hematopoietic stem and progenitor cells. CD133 has been utilized in a wide range of adult tumors and has become the most common marker used to identify pediatric TSC (Table 1) [20,22,23]. The first studies to utilize CD133 as a pediatric TSC marker occurred in brain tumors. Singh et al. purified CD133+ medulloblastoma (MB) TSC from patients’ tumors based on several functional criteria including a marked capacity for proliferation, a propensity for self-renewal, and capacity for asymmetric differentiation [24]. As a validation of the importance of TSC, they found that the self-renewal ability of the brain TSC was greatest in the most aggressive clinical samples of MB as compared with low-grade gliomas. Similarly, Hemmati et al. identified brain TSC in tumor samples from pediatric patients ranging in age from 15 months to six years who had MB, anaplastic astrocytoma, or glioblastoma multiforme (GBM) [25]. When cultured using stringent conditions in specially-formulated serum-free tissue culture medium with epidermal growth factor and basic fibroblast growth factor, tumor cells grew non-adherently in clumps of cells rather than as monolayers and cells in these tumor-derived “neurospheres” (Figure 1) expressed genes characteristic of neural stem cells including CD133, the transcription factor Sox2, and nuclear and cytoplasmic proteins musashi-1and bmi-1. More recent studies have used CD133 alone or in combination with nestin, an intermediate filament protein expressed in embryonic neuroglial cells, to isolate TSC in MB, to establish an anaplastic MB cell line with stem cell features, and to develop clinically relevant xenograft mouse models of MB and high-grade glioma [26-28]. CD133+ TSC have been identified in other pediatric brain tumors including ependymoma and atypical teratoid/rhabdoid tumor (AT/RT) [29-31]. The cell of origin of ependymomas may be the radial glia cells as tumor-derived spheres displayed an immunophenotype (CD133+, nestin+, radial glia marker RC2+, and brain-lipid binding protein (BLBP+)) similar to that of normal radial glia cells [29]. However, as will be detailed below, CD133 may not necessarily be the most accurate marker for tumor cells that display the functional characteristics that have come to be associated with TSC, and recently, several groups have suggested that CD15 (stage specific embryonic antigen 1 or SSEA-1), which is expressed on neural progenitor and stem cells, may be a better marker than CD133 of tumor-initiating cells in MB, glioma, and ependymoma [32-35].


Cancer Stem Cells and Pediatric Solid Tumors.

Friedman GK, Gillespie GY - Cancers (Basel) (2011)

(A) Glioblastoma multiforme cells grown as neurospheres in serum-free medium supplemented with epidermal growth factor and basic fibroblast growth factor. (B) Cells grown in DMEM with fetal bovine serum and L-glutamine.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3050504&req=5

f1-cancers-03-00298: (A) Glioblastoma multiforme cells grown as neurospheres in serum-free medium supplemented with epidermal growth factor and basic fibroblast growth factor. (B) Cells grown in DMEM with fetal bovine serum and L-glutamine.
Mentions: The most widely used cell surface molecule relied upon as a TSC marker is CD133 or prominin-1, a transmembrane protein with uncertain biological function that was initially discovered on hematopoietic stem and progenitor cells. CD133 has been utilized in a wide range of adult tumors and has become the most common marker used to identify pediatric TSC (Table 1) [20,22,23]. The first studies to utilize CD133 as a pediatric TSC marker occurred in brain tumors. Singh et al. purified CD133+ medulloblastoma (MB) TSC from patients’ tumors based on several functional criteria including a marked capacity for proliferation, a propensity for self-renewal, and capacity for asymmetric differentiation [24]. As a validation of the importance of TSC, they found that the self-renewal ability of the brain TSC was greatest in the most aggressive clinical samples of MB as compared with low-grade gliomas. Similarly, Hemmati et al. identified brain TSC in tumor samples from pediatric patients ranging in age from 15 months to six years who had MB, anaplastic astrocytoma, or glioblastoma multiforme (GBM) [25]. When cultured using stringent conditions in specially-formulated serum-free tissue culture medium with epidermal growth factor and basic fibroblast growth factor, tumor cells grew non-adherently in clumps of cells rather than as monolayers and cells in these tumor-derived “neurospheres” (Figure 1) expressed genes characteristic of neural stem cells including CD133, the transcription factor Sox2, and nuclear and cytoplasmic proteins musashi-1and bmi-1. More recent studies have used CD133 alone or in combination with nestin, an intermediate filament protein expressed in embryonic neuroglial cells, to isolate TSC in MB, to establish an anaplastic MB cell line with stem cell features, and to develop clinically relevant xenograft mouse models of MB and high-grade glioma [26-28]. CD133+ TSC have been identified in other pediatric brain tumors including ependymoma and atypical teratoid/rhabdoid tumor (AT/RT) [29-31]. The cell of origin of ependymomas may be the radial glia cells as tumor-derived spheres displayed an immunophenotype (CD133+, nestin+, radial glia marker RC2+, and brain-lipid binding protein (BLBP+)) similar to that of normal radial glia cells [29]. However, as will be detailed below, CD133 may not necessarily be the most accurate marker for tumor cells that display the functional characteristics that have come to be associated with TSC, and recently, several groups have suggested that CD15 (stage specific embryonic antigen 1 or SSEA-1), which is expressed on neural progenitor and stem cells, may be a better marker than CD133 of tumor-initiating cells in MB, glioma, and ependymoma [32-35].

Bottom Line: Recently, a subpopulation of cells, termed tumor-initiating cells or tumor stem cells (TSC), has been identified in many different types of solid tumors.Much of the research on TSC has focused on adult cancers.With considerable differences in tumor biology between adult and pediatric cancers, there may be significant differences in the presence, function and behavior of TSC in pediatric malignancies.

View Article: PubMed Central - PubMed

Affiliation: Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.

ABSTRACT
Recently, a subpopulation of cells, termed tumor-initiating cells or tumor stem cells (TSC), has been identified in many different types of solid tumors. These TSC, which are typically more resistant to chemotherapy and radiation compared to other tumor cells, have properties similar to normal stem cells including multipotency and the ability to self-renew, proliferate, and maintain the neoplastic clone. Much of the research on TSC has focused on adult cancers. With considerable differences in tumor biology between adult and pediatric cancers, there may be significant differences in the presence, function and behavior of TSC in pediatric malignancies. We discuss what is currently known about pediatric solid TSC with specific focus on TSC markers, tumor microenvironment, signaling pathways, therapeutic resistance and potential future therapies to target pediatric TSC.

No MeSH data available.


Related in: MedlinePlus