In the June 4th issue of Cell Stem Cell, A. P. Aiden et al. from Harvard University reported their study results on identifying transcriptional and epigenetic mechanisms which give rise to Wilms tumor formation. With a comparison of genome-wide chromatin profiling of cells derived from Wilms tumors, embryonic stem cells (ESCs), and normal kidney, the investigators found that large active chromatin domains normally regulating gene expression in ESCs were also expressed in Wilms cells. These genes were associated with kidney development as well as maintaining the adult renal stem cell compartment. Interestingly, the Wilms cells expressing the embryonic-like chromatin regulators maintain stem cells in the kidney compartment by silencing p16. The experimental data revealed that these "bivalent promoters" in Wilms tumor correlated to silencing genes during early stages of differentiation in kidney progenitors. The authors concluded from their experimental results which they suggest that "Wilms cells share a transcriptional and epigenetic landscape with normal renal stem cells, which is inherently susceptible to transformation and my represent a cell of origin for this disease" (i.e. cancer stem cells).

In the June 14th online edition of Stem Cells, K. Watanabe et al. from the National Institute of Health (Bethesda, MD), published their study results on the expression of Cripto-1 (CR-1) and cancer stem cells. The investigators noted that CR-1 is a GP1-linked glycoprotein which is expressed during early embryogenesis and in human embryonal carcinoma (EC) cells. With FACS analysis, the researchers found two subpopulations of EC expressing either CR-1^High or CR-1^Low from EC cell lines (NTERA2/D1). The subpopulation expressing CR-1High was more tumorigenic, formed spheres in vitro, and tumors in xenografts. The CR-1High cells were also shown to be pluripotent in which they expressed pluripotent transcription factors Oct4, Sox2, and Nanog. The study results also revealed that CR-1 expression in the EC cell lines was regulated by Smad2/3 via the autocrine feedback loop during upregulation of the transcription factors Oct4/Nanog. The authors concluded that "CR-1 expression is enriched in an undifferentiated, tumorigenic subpopulation and is regulated by key regulators of pluripotent stem cells."

In the June 10th issue of Cell Stem Cell, R. Pang et al. from The University of Hong Kong, identified in their published study results a subpopulation of CD26+ from primary and mestastatic colorectal tumors with cancer-initiating properties of cancer stem cells (CSCs). The investigators reported that these tumorigenic CSCs had the ability to self-renew and were CD133+. Additionally, the experimental data revealed that co-expression CD133 and CD44 surface markers enhanced tumorigenicity when the CSCs were serially passaged in a xenograft mouse model. However, in comparing differential expression of markers in metastatic colorectal cancers and primary tumors, cells expressing CD26 were found in both primary colorectal tumors and liver metastasis. The researchers also demonstrated that CD26+ cells had the capacity to form liver metastases when injected into the cerum of mice; irrespective of whether they CD133 or CD44. On the other hand, CD26- cells were not able to form liver metastasis regardless of CD133 or CD44 expression. Subcutaneous coinjection of CD26+ cells and normal human intestinal fibroblasts significantly enhanced liver metastasis in SCID mice. CD26+ CSCs showed enhanced chemoresistance. The authors concluded from their experimental observations that they "have uncovered a critical role of CSCs in the mestatic progression of cancer" which allows one to "predict metastasis based on analysis of CSC subsets in the primary tumor."

In the June 1st online edition of Stem Cells, N. Naka et al. from the Osaka Medical Center for Cancer and Cardiovascular Diseases (Japan) reported their experimental findings which suggested that synovial sarcoma (SS) may originate from dysregulated stem cells. The investigators noted that SS is a malignant tumor characterized by chromosomal translocation (X & 11) resulting in SS18-SSX fusion gene protein product. SS human cell lines were shown to form sarcospheres and tumors in serial xenografts as well as the ability to self-renew. Both the SS cell lines and15 primary human tumor specimens were found to express the pluripotent proteins, Oct3/4, Nanog, and Sox2. Moreover, the researchers were able to differentiate the SS cells into mesenchymal lineages such as osteocytes and chondrocytes. Silencing of SS18-SSX abrogated the ability to form sarcospheres in the SS cells in suspension and the cells formed an adherent monolayer in cell culture experiments. Cells derived from the monolayer cultures were able to differentiate into osteocytes, chondrocytes, adipocytes and macrophages. The authors concluded that their data suggest "that a human multipotent mesenchymal stem cell can serve as a cell of origin for SS and SS is a stem cell malignancy resulting from dysregulation of self-renewal and differentiation capacities driven by the SS18-SSX fusion protein."