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Glioblastoma Multiforme (GBM) is the most malignant adult glial tumor, and generally considered to be developed from the transformed neural stem (NSC) or progenitor cells. A subset of GBM develops from lower grade astrocytoma and can thus be clinically classified as “secondary”, while some GBMs occur with no prior evidence of a lower grade tumor and can be clinically classified as “primary”. Using a functional genomics approach, real-time quantitative RT-PCR, and immunostaining, we demonstrated that a subset of primary GBM tumors and their derived tumor lines express cellular and molecular markers that are associated with mesen chymal stem cells (MSC) and their differentiated lineage cell types. Tissue microarray analyses confirmed higher incidence in expression of MSC-associated markers in primary GBM compared to secondary GBM or normal brain tissue. When treated with adipogenic, osteogenic or chondrogenic induction media, primary GBM cell lines are capable of differentiating into multiple mesenchymal lineage cell types. These findings suggest that at least a subset of primary GBMs may use a MSC-like program to achieve malignant phenotype. To further characterize stem like-properties in primary GBM, serum-cultured GBM cells were switched to serum-free medium supplemented with fibroblast growth factor, epidermal growth factor and leukemia inhibitory factor. Induction and expansion of GBM spheres that co-express NSC (CD133, nestin) and MSC (CD105, collagen type I, YKL-40) surface markers were determined. To study the molecular properties and functional role of CD133+CD105+ GBM cells, we compared CD133+CD105+ enriched GBM population to CD133-CD105+GBM cells in their transcription profile, lineage plasticity, in-vitro clonogenesis, drug sensitivity, and intracranial tumorigenecity.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]