In the January 25th online edition of Oncogene, S. Peng et al. from Yale University School of Medicine reported their study results on isolating a subpopulation epithelial cancer stem cells (CSCs) from ovarian tumors. These CSCs were found to co-express the pluripotent transcription factor Oct4 and microRNA Lin28. Both of these factors along with Klf4, Nanog, c-Myc and Sox2 have been used in various combinations to reprogram adult somatic cells. The investigators noted that co-expression of the two proteins in primary tumor samples correlated with advanced stages of the cancer. Additionally, in vitro RNA interference experiments demonstrated that inhibiting expression of Lin28 and Oct4 resulted in significant reduction in cell growth and survival of the CSCs. The authors proposed that "Lin28 and Oct 4 may have important roles in the initiation and/or progression of epithelial ovarian cancer cells, and consequently may serve as important molecular diagnostics and/or therapeutic targets for the development of novel treatment strategies."

Scientists from The Scripps Research Institute, H. Wurdak et al., reported in the January 8th issue of Cell Stem Cell, their study results on the kinome-wide RNA interference screen for identifying factors affecting tumorigenic potential of brain tumor-initiating cells (BTICs/brain cancer stem cells) from primary glioblastoma multiforme (GBM) tumors. The study was based on the premise that BTICs share the same features as neural stem cells with respect to expressed markers such as Nestin and Sox2 and their capacity to self-renew and undergo multilineage differentiation. It was also noted bone morphogenetic proteins and distinct microRNAs were able to suppress tumorgenecity of BTICs by inducing differentiation. The investigators identified "several genes whose silencing induced differentiation of BTICs derived from multiple GBM patients." Of particular note, the experimental data showed that one candidate gene known as transformation/transcription domain-associated protein (TRRAP) whose expression was found to be crucial for maintaining tumorigenecity in GBM-derived. Silencing of TRAPP with four different shRNAs resulted in differentiation in all BTICs. Knockdown of TRAPP was also found to decrease BTIC self-renewal and increased sensitivity to temozolomide-induced apoptosis.

In the today's (January 12th) online edition of Cancer Research, T. Schatton et al. from Harvard University's Children's Hospital reported their study results demonstrating the immunomodulating activity of melanoma cancer stem cells (malignant melanoma initiating cells/MMICs). The investigators found that these tumorigenic ABCB5+ cells in vitro downregulate anti-tumor acitivity by inhibiting IL-2 -dependent T cell activation concomitant with the induction of regulatory T cells via the production of IL-10. Cells from both melanoma xenografts and clinical tumor specimens expressed the costimulatory molecules B7.2 and PD-1 (immunosuppress T cell activation). Immune activation experiments showed that MMICs (ABCB5+) inhibited mitogenic-dependent proliferative responses as well as IL-2 production in peripheral mononuclear cells than ABCB5- cells. Increased in the number of T regs were found to correlate with B7.2 signaling by MMICs. The authors concluded that their findings "identify novel T-cell functions of ABCB5+ melanoma subpopulations and suggest specific roles for these MMICs in the evasion of antitumor immunity and in cancer immunotherapeutic resistance."