CD133, CD15/SSEA-1, CD34 or side populations do not resume tumor-initiating properties of long-term cultured cancer stem cells from human malignant glio-neuronal tumors

Abstract

BackgroundTumor initiating cells (TICs) provide a new paradigm for developing original therapeutic strategies.MethodsWe screened for TICs in 47 human adult brain malignant tumors. Cells forming floating spheres in culture, and endowed with all of the features expected from tumor cells with stem-like properties were obtained from glioblastomas, medulloblastoma but not oligodendrogliomas.ResultsA long-term self-renewal capacity was particularly observed for cells of malignant glio-neuronal tumors (MGNTs). Cell sorting, karyotyping and proteomic analysis demonstrated cell stability throughout prolonged passages. Xenografts of fewer than 500 cells in Nude mouse brains induced a progressively growing tumor. CD133, CD15/LeX/Ssea-1, CD34 expressions, or exclusion of Hoechst dye occurred in subsets of cells forming spheres, but was not predictive of their capacity to form secondary spheres or tumors, or to resist high doses of temozolomide.ConclusionsOur results further highlight the specificity of a subset of high-grade gliomas, MGNT. TICs derived from these tumors represent a new tool to screen for innovative therapies.

Semaphorin 3A elevates endothelial cell permeability through PP2A inactivation

“…In this model, PP2A might protect VE-cadherin from S665 phosphorylation and internalisation in quiescent cells. markers, such as Nestin and Sox2, can self-renew and retain the ability to initiate and form a tumour mimicking the original (Galli et al, 2004;Patru et al, 2010;Singh et al, 2004;Yuan et al, 2004). In our study, we proposed that S3A is preferentially expressed by a small subpopulation of brain tumour cells (GSCs) that have endothelial progenitor properties and closely interact with endothelial cells (Calabrese et al, 2007;Ricci-Vitiani et al, 2010;Wang et al, 2010).…”

“…Glioma stem-like cell-secreted Semaphorin 3A remodels brain endothelial cell monolayers Because S3A may target different cell types and be produced within the tumour microenvironment (Acevedo et al, 2008;Catalano et al, 2006;Maione et al, 2009;Maione et al, 2012), we analysed its expression pattern in glioma cell lines and glioma stem-like cells (GSCs), isolated from high-grade brain tumours (Patru et al, 2010), by confocal microscopy, RT-PCR and immunoblotting ( Fig. 2A-D).…”

The miR 302-367 cluster drastically affects self-renewal and infiltration properties of glioma-initiating cells through CXCR4 repression and consequent disruption of the SHH-GLI-NANOG network

“…To identify miRNAs capable of suppressing GiCs stemness properties, we used two previously characterized GiCs primary lines, 14 TG1 and TG6, and took advantage of the ability of serum to induce stem cells differentiation. 14 Self-renewing TG cells were forced into a more differentiated non-stem-like state, by substituting the growth factors EGF and bFGF with 0.5% serum.…”

“…To identify miRNAs capable of suppressing GiCs stemness properties, we used two previously characterized GiCs primary lines, 14 TG1 and TG6, and took advantage of the ability of serum to induce stem cells differentiation. 14 Self-renewing TG cells were forced into a more differentiated non-stem-like state, by substituting the growth factors EGF and bFGF with 0.5% serum. After 4 days, the glial proteins GFAP and Olig2 were upregulated (Figures 1a and b) while the cells exhibited low levels of the stemness markers Oct-4, Nanog, (Supplementary Figure 1A), and of SHH clearly established as a major player in GiCs self-renewal 15 (Figures 1a and b).…”

DNA repair in cancer stem cells as a factor for glioma resistance to radiotherapy

“…(Singh et al, 2004) показали, что даже 10 2 CD133+ клеток достаточно для формирования опухолей при имплантации иммунодефицитным мышам, в то время как инъекция 10 5 CD133-клеток не обеспечивала образо-вания опухоли. Однако имеются также данные о том, что и CD133-клетки могут формировать нейросферы in vitro (Patru et al, 2010) и опухоли при имплантации крысам (Wang et al, 2008). Это свидетельствует о том, что CD133 не является универсальным маркером ОСК, и в настоящее время продолжается поиск маркеров этих клеток.…”