Cortical and Subventricular Zone Glioblastoma-Derived Stem-Like Cells Display Different Molecular Profiles and Differential In Vitro and In Vivo Properties

Tchoghandjian, Aurélie; Baeza-Kallee, Nathalie; Béclin, Christophe; Métellus, Philippe; Colin, Carole; Ducray, François; Adélaı̈de, José; Rougon, Geneviève; Figarella‐Branger, Dominique

doi:10.1245/s10434-011-2093-5

Cited by 35 publications

(49 citation statements)

References 29 publications

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“…Interestingly, Tchoghandjian and collaborators, observed similar infiltrative and multifocal clusters in vivo invasion patterns displayed by Mesenchymal and Neural GBM-derived stem-like cells, respectively [28]. The result that BCAN was found expressed at the highest level in PT5 and PT6, which we classified as Mesenchymal, is in apparent disagreement with previous studies [23,29].…”

Section: Discussioncontrasting

confidence: 81%

Identification of a novel set of genes reflecting different in vivo invasive patterns of human GBM cells

et al. 2012

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BackgroundMost patients affected by Glioblastoma multiforme (GBM, grade IV glioma) experience a recurrence of the disease because of the spreading of tumor cells beyond surgical boundaries. Unveiling mechanisms causing this process is a logic goal to impair the killing capacity of GBM cells by molecular targeting.We noticed that our long-term GBM cultures, established from different patients, may display two categories/types of growth behavior in an orthotopic xenograft model: expansion of the tumor mass and formation of tumor branches/nodules (nodular like, NL-type) or highly diffuse single tumor cell infiltration (HD-type).MethodsWe determined by DNA microarrays the gene expression profiles of three NL-type and three HD-type long-term GBM cultures. Subsequently, individual genes with different expression levels between the two groups were identified using Significance Analysis of Microarrays (SAM). Real time RT-PCR, immunofluorescence and immunoblot analyses, were performed for a selected subgroup of regulated gene products to confirm the results obtained by the expression analysis.ResultsHere, we report the identification of a set of 34 differentially expressed genes in the two types of GBM cultures. Twenty-three of these genes encode for proteins localized to the plasma membrane and 9 of these for proteins are involved in the process of cell adhesion.ConclusionsThis study suggests the participation in the diffuse infiltrative/invasive process of GBM cells within the CNS of a novel set of genes coding for membrane-associated proteins, which should be thus susceptible to an inhibition strategy by specific targeting.Massimiliano Monticone and Antonio Daga contributed equally to this work

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Section: Discussioncontrasting

confidence: 81%

Identification of a novel set of genes reflecting different in vivo invasive patterns of human GBM cells

et al. 2012

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“…In addition, H19 regulates the activity of transcriptional factor zinc finger protein GLI1 (GLI1), which serves a role in the development of astrocytoma. Abnormally high expression of GLI1 is typically detected in brain glioma, and the upregulation of GLI1 is associated with an increased cell proliferation index, pathology index and the recurrence of glioma (29).…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA Fer-1-like family member 4 is overexpressed in human glioblastoma and regulates the tumorigenicity of glioma cells

et al. 2017

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Abstract. Long non-coding RNA (lncRNA) is a class of regulative non-coding RNA that is >200 nucleotides in length. Previous studies have demonstrated that lncRNA Fer-1-like family member 4 (FER1L4) serves regulatory roles in tumor progression; however, its clinical significance in human neuroglioma remains unclear. In the present study, data from The Cancer Genome Atlas was mined in order to investigate the association between FER1L4 expression and prognosis in patients with glioma. A short interfering (si)RNA targeting FER1L4 was transfected into U373-MG and U251 glioma cell lines, and cell viability, invasion and apoptosis were examined using CCK-8, Transwell and Annexin V-fluorescein isothiocyanate/propidium iodide assays, respectively. FER1L4 was significantly upregulated in high-grade glioma compared with low-grade glioma. Additionally, high expression of FER1L4 significantly predicted poor prognosis in patients with glioma. The expression of FER1L4 in glioma cell lines was significantly higher compared with that in normal astrocytes. Furthermore, by downregulating FER1L4 using siRNA, the invasiveness and viability of the glioma cells significantly decreased, while apoptosis significantly increased. The findings from the present study indicate that FER1L4 serves a role in the occurrence and progression of glioma, and could be used as a prognostic biomarker for this disease.

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“…27 These cells were grown as floating spheres in serum-free medium supplemented with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) as previously described. 28 For GDC-0152 treatment experiments, cells were grown in the same medium on 10 μ g/ml poly-DL-ornithin in order to allow cells to attach to the plastic without differentiating.…”

Section: Methodsmentioning

confidence: 99%

Inhibitor of apoptosis protein expression in glioblastomas and their in vitro and in vivo targeting by SMAC mimetic GDC-0152

et al. 2016

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Glioblastomas (GBMs) are the most aggressive primary brain tumors in adult and remain a therapeutic challenge. Targeting key apoptosis regulators with the ultimate aim to restore apoptosis in tumor cells could be an interesting therapeutic strategy. The inhibitors of apoptosis proteins (IAPs) are regulators of cell death and represent attractive targets, especially because they can be antagonized by SMAC mimetics. In this study, we first investigated the expression of cIAP1, cIAP2, XIAP and ML-IAP in human GBM samples and in four different cell lines. We showed that all GBM samples and GBM cell lines expressed all these IAPs, although the expression of each IAP varied from one case to another. We then showed that high level of ML-IAP predicted worse progression-free survival and overall survival in both univariate and multivariate analyses in two independent cohorts of 58 and 43 primary human GBMs. We then used GDC-0152, a SMAC mimetic that antagonizes these IAPs and confirmed that GDC-0152 treatment in vitro decreased IAPs in all the cell lines studied. It affected cell line viability and triggered apoptosis, although the effect was higher in U87MG and GL261 than in GBM6 and GBM9 cell lines. In vivo, GDC-0152 effect on U87MG orthotopic xenografts was dose dependent; it postponed tumor formation and slowed down tumor growth, significantly improving survival of GBM-bearing mice. This study revealed for the first time that ML-IAP protein expression correlates with GBM patient survival and that its antagonist GDC-0152 improves outcome in xenografted mouse.

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Cortical and Subventricular Zone Glioblastoma-Derived Stem-Like Cells Display Different Molecular Profiles and Differential In Vitro and In Vivo Properties

Abstract: Altogether, our findings suggest that tumor location in addition to molecular signature influence tumor growth and migration pattern.

Cited by 35 publications

References 29 publications

Identification of a novel set of genes reflecting different in vivo invasive patterns of human GBM cells

Identification of a novel set of genes reflecting different in vivo invasive patterns of human GBM cells

Long non-coding RNA Fer-1-like family member 4 is overexpressed in human glioblastoma and regulates the tumorigenicity of glioma cells

Inhibitor of apoptosis protein expression in glioblastomas and their in vitro and in vivo targeting by SMAC mimetic GDC-0152

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