CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles.

By D. Beier, P. Hau, M. Proescholdt, A. Lohmeier, J. Wischhusen, P. Oefner, L. Aigner, A. Brawanski, U. Bogdahn, C. Beier. Cancer Research, 2007

1,177 citations recorded by the source corpus.

Although glioblastomas show the same histologic phenotype, biological hallmarks such as growth and differentiation properties vary considerably between individual cases. To investigate whether different subtypes of glioblastomas might originate from different cells of origin, we cultured tumor cells from 22 glioblastomas under medium conditions favoring the growth of neural and cancer stem cells (CSC). Secondary glioblastoma (n = 7)-derived cells did not show any growth in the medium used, suggesting the absence of neural stem cell-like tumor cells. In contrast, 11/15 primary glioblastomas contained a significant CD133(+) subpopulation that displayed neurosphere-like, nonadherent growth and asymmetrical cell divisions yielding cells expressing markers characteristic for all three neural lineages. Four of 15 cell lines derived from primary glioblastomas grew adherently in vitro and were driven by CD133(-) tumor cells that fulfilled stem cell criteria. Both subtypes were similarly tumorigenic in nude mice in vivo. Clinically, CD133(-) glioblastomas were characterized by a lower proliferation index, whereas glial fibrillary acidic protein staining was similar. GeneArray analysis revealed 117 genes to be differentially expressed by these two subtypes. Together, our data provide first evidence that CD133(+) CSC maintain only a subset of primary glioblastomas. The remainder stems from previously unknown CD133(-) tumor cells with apparent stem cell-like properties but distinct molecular profiles and growth characteristics in vitro and in vivo.

Subfields: Cancer Research, Genetics, Oncology

View Paper: https://www.semanticscholar.org/paper/bc4503e3b26cc829ed08ec47b3dcd911ff1d2ef4

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Genetics

In Oncology

Citations in the corpus

Integrin alpha 6 regulates glioblastoma stem cells (2010, background): “However, CD133 faces limitations as indicated by recent reports that show that CD133-negative GBM cells can form tumors (Beier et al., 2007; Joo et al., 2008; Wang et al., 2008a) and the expression of CD133 may be cell cycle regulated (Jaksch et al.”
Cancer stem cells in glioblastoma (2015, background): “It is nearly certain that CD133 is not universally informative in all tumors and has a false-negative rate for identifying CSCs (CD133-negative cells can be tumorpropagating in some tumors) (Beier et al. 2007).”
let-7 regulates self renewal and tumorigenicity of breast cancer cells. (2007, background): “Our results need to be considered in light of evidence for possible phenotypic heterogeneity of T-IC, as recently suggested for glioma (Beier et al., 2007) and of the heterogeneity of breast tumor cells that develop after tumor initiation secondary to additional mutations or epigenetic changes…”
Hypoxia-Inducible Factors Regulate Tumorigenic Capacity of Glioma Stem Cells (2009, background): “The role of HIF2a in tumors that are not driven by CD133 expression (Beier et al., 2007; Zheng et al., 2007; Wang et al., 2008) is still unresolved, but we did not observe HIF2a expression in a rat glioma cell line in which CD133-negative cells were reported to be tumorigenic (Zheng et al., 2007).”
SSEA-1 Is an Enrichment Marker for Tumor-Initiating Cells in Human Glioblastoma (2009, background): “These data, which are consistent with those of others (Beier et al., 2007; Joo et al., 2008; Ogden et al., 2008; Wang et al., 2008), suggest that CD133 may not be a universal enrichment marker for TSC/TIC in GBMs.”
The therapeutic promise of the cancer stem cell concept. (2010, background): “found that CD133– glioma cells also contain subpopulations capable of initiating tumors, termed CD133– glioma CSCs (44).”
Cancer stem cells: impact, heterogeneity, and uncertainty. (2012, background): “Yet subsequent studies found tumorigenic activity among both CD133+ and CD133 brain tumor cells (Beier et al., 2007; Chen et al., 2010; Joo et al., 2008; Wang et al., 2008).”
Malignant astrocytic glioma: genetics, biology, and paths to treatment. (2007, background): “There are, however, a number of reports that suggest a less clear distinction between the ability of CD133 and CD133 cells to form orthotopic tumors (Bao et al. 2006b; Sakariassen et al. 2006; Beier et al. 2007; Zheng et al. 2007).”
Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. (2009, background): “CD133 wasnot present on all GNS cell lines, confirming that this marker does not universally identify tumorigenic cells in malignant glioma (Beier et al., 2007).”