In the November 23rd online edition of Stem Cells, A. C. de Carvalho et al. from Henry Ford Hospital, published the results of their on the use of a neurosphere assay to generate a subpopulation of gliosarcoma (GS) stem cells from primary surgical specimens. The investigators found that cells cultured from gliablastoma (GBM) and GS tumors expressed Sox2, Msi1 and Nestin. Interestingly, GS neurospheres did not expressed the CD133 stem cell marker. However, cells from both GS and GBM neurospheres were tumorigenic in xenografts. Of particular note, the investigators reported that GS serum cultures (low passage) retained their stem cell phenotype both in forming neurospheres and tumors. This observation was in contrast to long-term propagation of GBM cells in serum in which the cells lost their tumorigenic potential as well as the ability to form neurospheres. The investigators also found that the GS cell cultures "exhibited biphasic glial and mesenchymal components" which they believed would provide a model for investigating mesenchymal differentiation in GBMs.

In the November 10th online edition of Stem Cells, X. Fan et al. from the Univ. of Michigan Medical School published their study results whereby blocking Notch signaling pathway in glioblastoma (GBM)-derived cancer stem cells inhibits tumor growth and proliferation of "stem-like cancer cells." The investigators based their study on the observation that cancer stem cells (CSCs) from GBM patients had higher Notch activity. With a Notch inhibitor (gamma-secretase/GSIs), the researchers found reduced neurosphere growth and decreased clonogeneic potential of the GBM-derived stem cells in vitro. The experimental results also showed that GSI reduced expression of CD133, Nestin, Bm`, and Olig2 (putative glioblastoma cancer stem cell markers) in the cancer stem cell population. GBM cells pretreated with GSI were found to block tumor growth when implanted into animals. The investigators observed that GSI-treated cells appeared to have reduced number of stem-like cancer cells which they found was associated with reduced proliferation and increased apoptosis due to decreased Akt and STAT3 phosphorylation. The authors concluded from their experimental observations that "GSIs may be useful as chemotherapeutic reagents to target CSCs in malignant gliomas."

Japanese scientists, H. Ikushima et al., from the University of Tokyo reported http://www.cell.com/cell-stem-cell/abstract/S1934-5909%2809%2900402-0 in the November 6th issue of Cell Stem Cell their study results on the the mechanism in which autocrine TGF-β signaling has a major role in maintaining stemness of glioma-initiating cells (GICs/glioma cancer stem cells). The investigators found that TGF-β indirectly induced expression of the pluripotent gene, Sox2, by targeting Sox4. Experiments were conducted which demonstrated that inhibitors of TGF-β signaling resulted in a loss in the tumorigenic potential of GICs. The study results further revealed that inhibitors of TGF-β signaling promoted differentiation in glioma-initiating stem cells. The authors concluded that a new therapeutic strategy for treating malignant glioma may be the use of inhibitors that block the TGF-β-Sox4-Sox2 pathway.