CD133/prominin1 is prognostic for GBM patient's survival, but inversely correlated with cysteine cathepsins' expression in glioblastoma derived spheroids

Ardebili, Seyed Y.; Zajc, Irena; Gole, Boris; Campos, Benito; Herold‐Mende, Christel; Drmota, Sara; Lah, Tamara T.

doi:10.2478/v10019-011-0015-6

Cited by 36 publications

(38 citation statements)

References 39 publications

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“…The data suggested that the number of GSCs was positively correlated to the number of tumor cells, confirming the role of GSCs in tumorigenesis. Previous clinical researches have also documented that high CD133 mRNA expression in patients was a significant prognostic factor for adverse overall survival (Ardebili et al 2011;Metellus et al 2011).…”

Section: Discussionmentioning

confidence: 98%

Phosphoribosylpyrophosphate Synthetase 1 Knockdown Suppresses Tumor Formation of Glioma CD133+ Cells Through Upregulating Cell Apoptosis

Yan

Cao

et al. 2016

J Mol Neurosci

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Relapse is the main cause of mortality in patients with glioblastoma multiforme (GBM). Treatment options involve surgical resection followed by a combination of radiotheraphy and chemotherapy with temozolomide. Several genes and genetic pathways have been identified to contribute to therapeutic resistance, giving rise to recurrence of the malignancy. In the last decades, glioma stem cells (GSCs) with the capacity of self-renewal have been demonstrated to maintain tumor propagation and treatment resistance. Here, we isolated CD133-positive (CD133+) and CD133-negative (CD133-) cells from glioblastoma U98G and U87MG cell lines. The role of phosphoribosylpyrophosphate synthetase 1 (PRPS1), which catalyzes the first step of the synthesis of nucleotide, in proliferation and apoptosis was investigated. We found that PRPS1 had a remarkable effect on cell proliferation and sphere formation in both CD133+ and CD133- cells. Compared to CD133- cells, CD133+ cells exhibited more significant results in cell apoptosis assay. CD133+ T98G and U87MG cells were used in xenograft mouse model of tumor formation. Interestingly, the mice implanted with PRPS1 knockdown T98G or U87MG stem cells exhibited prolonged survival time and reduced tumor volume. By immunostaining caspase-3 in tumor tissues of these mice, we demonstrated that the apoptotic activities in tumor cells were positively correlated to the survival time but negatively correlated to PRPS1 expression. Our results indicate that PRPS1 plays an important role in proliferation and apoptosis in GSCs and provide new clues for potential PRPS1-targeted therapy in GBM treatment.

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Section: Discussionmentioning

confidence: 98%

Phosphoribosylpyrophosphate Synthetase 1 Knockdown Suppresses Tumor Formation of Glioma CD133+ Cells Through Upregulating Cell Apoptosis

Yan

Cao

et al. 2016

J Mol Neurosci

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“…Main characteristics of these ten eligible studies were summarized in Table 1. The total number of patients was 715, ranging from 24 to 239 patients per study [14][15][16][17][18][19][20][21][22][23]. Nine articles were on overall survival [14][15][16][17][19][20][21][22][23], and seven studies were about progression-free survival [14-18, 21, 22].…”

Section: Study Selection and Description Of Included Studiesmentioning

confidence: 99%

“…After reviewing the abstracts, only 25 studies were preliminarily included and were further assessed by reading full text [14][15][16][17][18][19][20][21][22][23][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42]. Fifteen studies were then excluded for other types of gliomas or the lack of usable data [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42], and ten studies were finally included into the meta-analysis [14][15][16][17][18][19][20][21][22][23]. Those t...…”

Section: Study Selection and Description Of Included Studiesmentioning

confidence: 99%

“…CD133 has been found to be a putative marker of cancer stem cells in various cancers [9][10][11][12], and it also has been identified as a putative stem cell marker in gliomas [13]. Several clinical observational studies were performed to evaluate the association of CD133 expression with the prognosis of glioblastoma patients, but no consistent finding was available [14][15][16][17][18][19][20][21][22][23]. Therefore, the prognostic significance of CD133 expression in glioblastoma remained controversial.…”

Section: Introductionmentioning

confidence: 99%

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High CD133 Expression Is Associated with Worse Prognosis in Patients with Glioblastoma

Zhang

Chen

et al. 2015

Mol Neurobiol

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The CD133 antigen has been identified as a putative stem cell marker in gliomas. However, the prognostic significance of CD133 expression in glioblastoma patients remained controversial. A meta-analysis of published data was performed to comprehensively assess the prognostic role of CD133 expression in glioblastoma patients. Publications assessing the prognostic significance of CD133 expression in glioblastoma patients were identified in PubMed, Embase, and Web of Science up to November 2014. The pooled hazard ratio (HR) with 95% confidence interval (95% CI) was calculated using meta-analysis to evaluate the prognostic significance of CD133 expression in glioblastoma. Ten studies with a total of 715 glioblastoma patients were included into the meta-analysis. Overall, high CD133 expression was associated with poorer overall survival in patients with glioblastoma (HR = 1.96, 95% CI 1.46-2.64, P < 0.001). In addition, high CD133 expression was also associated with poorer progression-free survival in patients with glioblastoma (HR = 2.03, 95% CI 1.43-2.88, P < 0.001). Meta-analyses of studies with high quality showed that high CD133 expression was associated with both poorer overall survival (HR = 2.39, 95% CI 1.77-3.23, P < 0.001) and poorer progression-free survival (HR = 2.17, 95% CI 1.60-2.94, P < 0.001) in patients with glioblastoma. Meta-analysis of studies with adjusted estimates further showed that high CD133 expression was an independent prognostic factor of glioblastoma. High CD133 expression is associated with worse prognosis in patients with glioblastoma. More prospective studies with well-design are needed to confirm this finding.

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“…3 The importance of CD133 as a marker of tumor aggressiveness was corroborated by the correlation between CD133 expression in brain tumors and a poor clinical prognosis. [4][5][6] However, later studies revealed that CD133-negative cells can give rise to CD133-positive cells 7-9 and that both CD133-positive and CD133-negative GBM cells can initiate the development of highly aggressive tumors. 10 Moreover, diverse GCSC types -all capable of self-renewal and tumor initiation -coexist within the same GBM.…”

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confidence: 99%

Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells: prognostic significance and biological impact

et al. 2015

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Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemotherapy, and radiation therapy. Unfortunately, this standard therapy does not target glioma cancer stem cells (GCSCs), a subpopulation of GBM cells that can give rise to recurrent tumors. GBMs express human cytomegalovirus (HCMV) proteins, and previously we found that the level of expression of HCMV immediate-early (IE) protein in GBMs is a prognostic factor for poor patient survival. In this study, we investigated the relation between HCMV infection of GBM cells and the presence of GCSCs. Primary GBMs were characterized by their expression of HCMV-IE and GCSCs marker CD133 and by patient survival. The extent to which HCMV infection of primary GBM cells induced a GCSC phenotype was evaluated in vitro. In primary GBMs, a large fraction of CD133-positive cells expressed HCMV-IE, and higher co-expression of these two proteins predicted poor patient survival. Infection of GBM cells with HCMV led to upregulation of CD133 and other GSCS markers (Notch1, Sox2, Oct4, Nestin). HCMV infection also promoted the growth of GBM cells as neurospheres, a behavior typically displayed by GCSCs, and this phenotype was prevented by either chemical inhibition of the Notch1 pathway or by treatment with the anti-viral drug ganciclovir. GBM cells that maintained expression of HCMV-IE failed to differentiate into neuronal or astrocytic phenotypes. Our findings imply that HCMV infection induces phenotypic plasticity of GBM cells to promote GCSC features and may thereby increase the aggressiveness of this tumor. GBM is the most prevalent and the most aggressive primary malignancy of the central nervous system in adults. It is a highly vascularized and infiltrating tumor, rarely cured and prone to recurrence. The median duration of survival after diagnosis is less than 15 months, despite aggressive therapy consisting of surgical resection and concomitant radiotherapy and chemotherapy. 1 Surgical resection of GBMs is typically incomplete, as they are located in the brain and are highly infiltrative. Postoperative radiotherapy and chemotherapy fail to eradicate all remaining GBM cells. Thus, a breakthrough in identifying a new treatment option leading to a cure of this disease is still lacking.GBMs contain a subpopulation of highly tumorigenic cells with unlimited capacity for self-renewal that are commonly resistant to standard therapy. Phenotypically and functionally, these cells resemble neural stem cells and, when implanted in immunodeficient mice, can generate new tumors. As a result, they are referred to as glioma cancer initiating cells or glioma cancer stem cells (GCSCs) (reviewed in Lima et al. 2 ).Because of their apparent pivotal role in gliomagenesis and tumor recurrence after therapy, GCSCs are a major focus of research whose ultimate goal is to identify more effective therapies for GBM patients.GCSCs were first identified by their surface expression of CD133, based on the findings that these cells grow as neurospheres under nonadher...

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CD133/prominin1 is prognostic for GBM patient's survival, but inversely correlated with cysteine cathepsins' expression in glioblastoma derived spheroids

Cited by 36 publications

References 39 publications

Phosphoribosylpyrophosphate Synthetase 1 Knockdown Suppresses Tumor Formation of Glioma CD133+ Cells Through Upregulating Cell Apoptosis

Phosphoribosylpyrophosphate Synthetase 1 Knockdown Suppresses Tumor Formation of Glioma CD133+ Cells Through Upregulating Cell Apoptosis

High CD133 Expression Is Associated with Worse Prognosis in Patients with Glioblastoma

Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells: prognostic significance and biological impact

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