Glioblastoma-derived stem cell-enriched cultures form distinct subgroups according to molecular and phenotypic criteria

• Published in: Oncogene Vol. 27; no. 20; pp. 2897 - 2909
• Main Authors: Günther, H S, Schmidt, N O, Phillips, H S, Kemming, D, Kharbanda, S, Soriano, R, Modrusan, Z, Meissner, H, Westphal, M, Lamszus, K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2008; Nature Publishing; Nature Publishing Group
• Subjects: Adult; Aged; Aged, 80 and over; Animals; Apoptosis; Biological and medical sciences; Brain cancer; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain tumors; Cell Biology; Cell culture; Cell Culture Techniques; Cell Line, Tumor; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; DNA microarrays; Extracellular matrix; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Genetic aspects; Glioblastoma; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; Glioblastoma multiforme; Glioma; Glioma cells; Health aspects; Human Genetics; Humans; Internal Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Nude; Middle Aged; Molecular and cellular biology; Neoplastic Stem Cells - classification; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Neural stem cells; Neurology; Oncology; original-article; Phenotype; Phenotypes; Risk factors; Stem cells; Therapeutic targets; Tumor cells; Tumor Cells, Cultured; Tumorigenicity; Tumors of the nervous system. Phacomatoses; Germany; glioma; pathway; neural stem cell; microarray; neurosphere; Cell culture; Nervous system diseases; Stem cell; Glioblastoma; Malignant tumor; Microarray; Carcinogenesis; Malignant glioma; Central nervous system disease; Cancer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1210949

Tumor cells with stem cell-like properties can be cultured from human glioblastomas by using conditions that select for the expansion of neural stem cells. We generated cell lines from glioblastoma specimens with the goal to obtain model systems for glioma stem cell biology. Unsupervised analysis of the expression profiles of nine cell lines established under neural stem cell conditions yielded two distinct clusters. Four cell lines were characterized by the expression of neurodevelopmental genes. They showed a multipotent differentiation profile along neuronal, astroglial and oligodendroglial lineages, grew spherically
in vitro
, expressed CD133 and formed highly invasive tumors
in vivo
. The other five cell lines shared expression signatures enriched for extracellular matrix-related genes, had a more restricted differentiation capacity, contained no or fewer CD133
+
cells, grew semiadherent or adherent
in vitro
and displayed reduced tumorigenicity and invasion
in vivo
. Our findings show that stable, multipotent glioblastoma cell lines with a full stem-like phenotype express neurodevelopmental genes as a distinctive feature, which may offer therapeutic targeting opportunities. The generation of another distinct cluster of cell lines showing similarly homogeneous profiling but restricted stem cell properties suggests that different phenotypes exist, each of which may lead to the typical appearance of glioblastoma.