Oct4 is expressed in human gliomas and promotes colony formation in glioma cells

Du, Zhanhui; Jia, Dongyu; Liu, Shangming; Wang, Fuwu; Li, Gang; Zhang, Yanmin; Cao, Xinmin; Ling, Eng‐Ang; Hao, Aijun

doi:10.1002/glia.20800

Cited by 145 publications

(142 citation statements)

References 43 publications

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“…1). The mRNA expression of markers of differentiation supported this observation, since expression of octamer-4 (Oct-4), a marker of embryonic stem cells and a transcription factor that is able to induce pluripotent cells [19], was observed only in spheres, whereas the attached population presented more expression of GLAST, a marker for differentiated glial cells and of CAMKII, a neuronal marker (Fig. 1e).…”

Section: Characterization Of a Tumor Stem Cell Population In The U87 supporting

confidence: 53%

Extracellular ATP reduces tumor sphere growth and cancer stem cell population in glioblastoma cells

Ledur

Villodre

Paulus

et al. 2011

Purinergic Signalling

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Glioblastoma is the most aggressive tumor in the CNS and is characterized by having a cancer stem cell (CSC) subpopulation essential for tumor survival. The purinergic system plays an important role in glioma growth, since adenosine triphosphate (ATP) can induce proliferation of glioma cells, and alteration in extracellular ATP degradation by the use of exogenous nucleotidases dramatically alters the size of gliomas in rats. The aim of this work was to characterize the effect of the purinergic system on glioma CSCs. Human U87 glioma cultures presented tumor spheres that express the markers of glioma cancer stem cells CD133, Oct-4, and Nanog. Messenger RNA of several purinergic receptors were differently expressed in spheres when compared to a cell monolayer not containing spheres. Treatment of human gliomas U87 or U343 as well as rat C6 gliomas with 100 μM of ATP reduced the number of tumor spheres when grown in neural stem cell medium supplemented with epidermal growth factor and basic fibroblast growth factor. Moreover, ATP caused a decline in the number of spheres observed in culture in a dose-dependent manner. ATP also reduces the expression of Nanog, as determined by flow cytometry, as well as CD133 and Oct-4, as analyzed by flow cytometry and RT-PCR in U87 cells. The differential expression of purinergic receptor in tumor spheres when compared to adherent cells and the effect of ATP in reducing tumor spheres suggest that the purinergic system affects CSC biology and that ATP may be a potential agonist for differentiation therapy.

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Section: Characterization Of a Tumor Stem Cell Population In The U87 supporting

confidence: 53%

Extracellular ATP reduces tumor sphere growth and cancer stem cell population in glioblastoma cells

Ledur

Villodre

Paulus

et al. 2011

Purinergic Signalling

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“…Therefore, analysis of the expression and significance of these genes in gliomas may aid in the understanding of the tumorigenesis and progression of gliomas. the significant role of oct4 and soX2 in gliomas has been reported (5,29). nAnog is a key stemness gene that is crucial for maintaining the biological properties of escs (34).…”

Section: Discussionmentioning

confidence: 93%

“…the cancer stem cell (csc) theory of tumorigenesis assumes the possibility of the identification of a small group of tumor cells responsible for the occurrence, growth, and recurrence of tumors in different types of cancers including gliomas (2)(3)(4). therefore, cscs are likely to be the most relevant targets in eradicating tumors, and further studies on the characterization of cscs may contribute to a more effective treatment of tumors (5). one promising approach is to target core stemness genes which are well known for playing important roles in the biological properties of escs.…”

Section: Introductionmentioning

confidence: 99%

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Expression of NANOG in human gliomas and its relationship with undifferentiated glioma cells

Niu

2011

Oncol Rep

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Abstract. stemness genes, including nAnog, which have been reported to play a significant role in embryonic stem cells (ESCs), are purported to be expressed in specific human tumor types. In the present study, we explored the expression of nAnog in gliomas to demonstrate its key roles in maintaining the undifferentiated state of glioma cells. Brain tumor stem cells (Btscs) were isolated from the human glioma cell line U87 and cultured in simplified serum-free medium. Significantly higher NANOG mRNA and protein expression levels were demonstrated in U87 parental attached cells and suspended Btscs as well as in 69 glioma specimens of different pathological grades. the relative levels of nAnog mrnA and protein expression were higher in the Btscs as compared to those in the U87 parental attached cells and were significantly positively correlated with pathological grade. the coexpression and relationship of nAnog, cD133 and gFAp in situ in the cellular levels was determined through double-label immunohistochemical staining in the gliomas. A positive correlation of nAnog and cD133 expression with pathological grade of the samples was noted, while nAnog and gFAp expression correlated negatively with the pathological grade (p<0.01). overexpression of nAnog in gliomas and its close relationship with the undifferentiated state of glioma cells in vivo and in vitro indicated that nAnog may contribute to the existence of Btscs and may be related to tumorigenesis of the cerebrum by maintaining the undifferentiated state of glioma cells, which provides a foundation to further explore its role in the biological behavior of gliomas.

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“…Many markers potentially specific for GSCs have been proposed such as A2B5 cell surface ganglioside epitope (A2B5) [26,27], aldehyde dehydrogenase (ALDH) [28], BMI1 polycomb ring finger oncogene (BMI1) [29,30], fucosyltransferase 4 (FUT4) (CD15) [31], Thy-1 cell surface antigen (Thy-1) (CD90) [32], prominin-1 (PROM1) (CD133) [5,6], chemokine (C-X-C motif) receptor 4 (CXCR4) [33], inhibitor of DNA binding 1 (ID1) [34], integrin α6 (ITGA6) [35], L1 cell adhesion molecule (L1CAM) [36], maternal embryonic leucine zipper kinase (MELK) [37], musashi-1 (msi1) [38], nestin (NES) [38][39][40], octamer-binding transcription factor 4 (OCT4) [41], OLIG2 [42] and SOX2 [38,[43][44][45]. Among these, much attention has been given to CD133, which is currently used to identify and isolate GSCs [40,43,[46][47][48][49][50].…”

Section: Discussionmentioning

confidence: 99%

Identification of OLIG2 as the most specific glioblastoma stem cell marker starting from comparative analysis of data from similar DNA chip microarray platforms

et al. 2014

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Despite advances in surgical and adjuvant treatments, overall survival of glioblastoma (GBM) patients remains poor. The cancer stem cell concept suggests that a rare stem cell population, called glioma stem cells (GSCs), has high ability to self-renewal leading to recurrence in GBM. The identification of specific markers of GSCs would provide a powerful tool to detect and to characterise them in order to develop targeted therapies. We carried out a comparative analysis based on the identification of inter-study concordances to identify the genes that exhibit at best differential levels of expression between GSC-enriched cell cultures and differentiated tumour cell cultures from independent studies using DNA chip microarray technologies. We finally studied the protein expression of the marker we considered the most specific by immunohistochemistry and semi-quantitative analysis on a retrospective series of 18 GBMs. Of the selected studies, 32 genes were retained. Among them, eight genes were identified to be overexpressed in GSC-enriched cultures compared to differentiated tumour cell cultures. Finally, among the eight genes, oligodendrocyte lineage transcription factor 2 (OLIG2) was characterised by the most different expression level in the "GSC model" compared to the "differentiated tumour cells model". Our approach suggests that OLIG2 is the most specific GSC marker; additional investigations with careful considerations about methodology and strategies of validation are, however, mandatory.

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Oct4 is expressed in human gliomas and promotes colony formation in glioma cells

Cited by 145 publications

References 43 publications

Extracellular ATP reduces tumor sphere growth and cancer stem cell population in glioblastoma cells

Extracellular ATP reduces tumor sphere growth and cancer stem cell population in glioblastoma cells

Expression of NANOG in human gliomas and its relationship with undifferentiated glioma cells

Identification of OLIG2 as the most specific glioblastoma stem cell marker starting from comparative analysis of data from similar DNA chip microarray platforms

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