In June 5th issue of Cell Stem Cells, S.M. Pollard et al. from University of Cambridge (UK) published their experimental data from their proof-of-principle study on analyzing adherent cell cultures derived from various human glioma cell lines. Because of the hierarchical cellular organization of human brain tumors, the investigators proposed that in vitro expansion of brain tumor cell lines may provide a model for studying putative cancer stem cells. From adherent cell lines from malignant gliomas, the researchers demonstrated that the cells were able to produce high-grade gliomas in xenotransplants. Gene expression profiling of the adherent cells revealed gene expression signatures and differentiation patterns associated with neural progenitor cells. Live cell imaging-based chemical screens showed that glioma neural stem cell (GNS) exhibited differential sensitivity to different approved drugs (450-FDA approved drugs). As opposed to neurospheres, the authors proposed that adherent glioma neural stem cell lines may offer an alternative for studying the behaviour and properties of cancer stem cells.

Scientists from Duke Univ. Medical Ctr., Z. Li et al., reported in the June 2nd issue of Cancer Cell their study results on hypoxic-inducible factor 2α (HIF 2α) and other HIF-regulated genes are preferentially expressed glioma stem cells (GSCs) compared to non-stem tumor cells. The experimental data showed that in primary tumor isolates, HIF 2α is co-expressed with cancer stem cell markers. In vitro studies targeting HIFs inhibited GSC proliferation, self-renewal, and survival as well as blocking its tumorigenic potential in vivo. Bioinformatic analysis demonstrated a correlation between poor prognosis in glioma patient survival and HIF 2α expression. The authors concluded from their experimental data that "GSCs differentially respond to hypoxia with distinct HIF patterns, and HIF 2α might represent a promising target for antiglioblastoma therapies."

Harvard Medical School scientists, S. R. Viswanathan et al., reported in a letter in the May 31st online edition of Nature Genetics their findings on Lin28 repressing the activity of the let-7 family of miRNAs and thereby promoting oncogenesis. The investigators found that both Lin28 and Lin28b block let-78 precursors from forming mature miRNAs. This observation suggested that overexpression of Lin28 may result in cellular transformation by derepressing oncogenes such as HMGA2, K-Ras and c-Myc (targets of let-7). In both primary human tumor isolates and human cancer cell lines, the researchers found overexpression of both Lin28 and Lin28b in 15% of the samples. In vitro analysis also demonstrated that overexpression of Lin28 facilitates cellular transformation concomitant with association of advanced disease across multiple tumor types. The authors concluded that their study results "provides a mechanism for the coordinate repression of let-7 miRNAs observed in a subset of human cancers, and associates activation of Lin28 and Lin28b with poor clinical prognosis."