Volume 2.27 | Jul 10

Cancer Stem Cell News 2.27 July 10, 2013
Cancer Stem Cell News
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TOP STORY
The Oncogenic MicroRNA miR-22 Targets the TET2 Tumor Suppressor to Promote Hematopoietic Stem Cell Self-Renewal and Transformation
Researchers showed that microRNA (miR)-22 is upregulated in myelodysplastic syndrome (MDS) and leukemia and its aberrant expression correlates with poor survival. To explore its role in hematopoietic stem cell function and malignancy, they generated transgenic mice conditionally expressing miR-22 in the hematopoietic compartment. These mice displayed reduced levels of global 5-hydroxymethylcytosine and increased hematopoietic stem cell self-renewal accompanied by defective differentiation. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract
Learn More: Column-Free Enrichment of Mouse Mammary Stem & Progenitor Cells
 
PUBLICATIONS (Ranked by impact factor of the journal)
Loss of Corepressor PER2 under Hypoxia Up-Regulates OCT1-Mediated EMT Gene Expression and Enhances Tumor Malignancy
The authors found that loss of the circadian clock gene Period2 (PER2) enhanced invasion and activated expression of epithelial-mesenchymal transition genes including TWIST1, SLUG, and SNAIL. This finding was corroborated by clinical observation that PER2 down-regulation was associated with poor prognosis in breast cancer patients. [Proc Natl Acad Sci USA] Abstract

ANTXR1, a Stem Cell Enriched Functional Biomarker, Connects Collagen Signaling to Cancer Stem-Like Cells and Metastasis in Breast Cancer
The anthrax toxin receptor ANTXR1 has been identified as a functional biomarker of normal stem cells and breast cancer stem-like cells. Primary stem cell-enriched basal cells (CD49f+/EpCAM-/Lin-) expressed higher levels of ANTXR1 compared to mature luminal cells. CD49f+/EpCAM-, CD44+/EpCAM-, CD44+/CD24- or ALDEFLUOR-positive subpopulations of breast cancer cells were enriched for ANTXR1 expression. CD44+/CD24-/ANTXR1+ cells displayed enhanced self-renewal as measured by mammosphere assay compared to CD44+/CD24-/ANTXR1- cells. [Cancer Res] Abstract

Distinct FAK Activities Determine Progenitor and Mammary Stem Cell Characteristics
Researchers showed that conditional deletion of focal adhesion kinase (FAK) in embryonic mammary epithelial cells decreases luminal progenitors (LPs) and basal mammary stem cells (MaSCs), reducing their colony-forming and regenerative potentials in a cell autonomous manner. In contrast to the general inhibitory effect of FAK attenuation, inhibitors of FAK kinase preferentially inhibited proliferation and tumorsphere formation of LP-like, but not MaSC-like, human breast cancer cells. [Cancer Res] Abstract

Expression of FUS-CHOP Fusion Protein in Immortalized/Transformed Human Mesenchymal Stem Cells Drives Mixoid Liposarcoma Formation
Investigators report that FUS-CHOP, a hallmark fusion gene in mixoid liposarcoma (MLS), has an instructive role in lineage commitment, and its expression in human mesenchymal stromal/stem cells (hMSCs) sequentially immortalized/transformed with up to 5 oncogenic hits (p53 and Rb deficiency, hTERT over-expression, c-myc stabilization and H-RASv12 mutation) drives the formation of serially transplantable MLS. This is the first model of sarcoma based on the expression of a sarcoma-associated fusion protein in hMSC, and allowed the authors to unravel the differentiation processes and signaling pathways altered in the MLS-initiating cells. [Stem Cells] Abstract

Targeting Cancer Stem Cells Expressing an Embryonic Signature with Anti-Proteases to Decrease Their Tumor Potential
Scientists showed that human immunodeficiency virus-protease inhibitors specifically target cancer stem cells expressing an embryonic signature derived from tumors with distinct origins. They reduced proliferation in a dose-dependent manner with a higher specificity as compared with the total population of cancer cells and/or healthy stem cells, and they were efficient in inducing cell death. [Cell Death Dis] Full Article

The Secretome of Colon Cancer Stem Cells Contains Drug-Metabolizing Enzymes
The contribution of cancer stem cells (CSCs) to drug-resistance in colorectal cancer is unclear and CSC-intrinsic drug-resistance mechanisms are ill-defined. Researchers addressed these issues by proteomic analysis of the secretomes of CSCs and isogenic differentiated tumor cells isolated from three distinct metastasized colon tumors. [J Proteomics] Abstract

Cytomegalovirus pp71 Protein Is Expressed in Human Glioblastoma and Promotes Pro-Angiogenic Signaling by Activation of Stem Cell Factor
Human cytomegalovirus (HCMV) infection is present in >90% of glioblastoma multiformes (GBMs), although the role the virus plays in GBM pathogenesis is unclear. Investigators report that HCMV pp71, a viral protein previously shown to promote cell cycle progression, is present in a majority of human GBMs and is preferentially expressed in the CD133+, cancer stem-like cell population. [PLoS One] Full Article

Comparative Proteomics of Glioma Stem Cells and Differentiated Tumor Cells Identifies S100A9 as a Potential Therapeutic Target
Researchers analyzed differentially expressed proteins between glioma stem cells and differentiated tumor cells isolated from the human glioma cell line, U251, via iTRAQ-tagging combined with two dimensional liquid chromatography tandem MS analysis to identify proteins correlated with specific features of cancer stem cells. [J Cell Biochem] Abstract

Culture Human Glioma-Derived Tumorspheres with NeuroCult™ - View Publications
 
REVIEWS
The Yin and Yang of Intestinal (Cancer) Stem Cells and Their Progenitors
The delineation of the active pathways in the intestinal epithelium together with the development of molecular techniques to prove stemness laid the grounds for the identification of the intestinal stem cell. In vitro systems and transgenic mouse models broaden our knowledge on the role of the stem cell niche and those cells that re-establish homeostasis after perturbation of the system. These insights expedited also research on the role of normal adult stem cells in cancer initiation and the factors influencing the maintenance of cancer stem cells. [Stem Cells] Abstract | Full Article

The Variety of Leukemic Stem Cells in Myeloid Malignancy
Human acute myeloid leukemias are sustained by leukemic stem cells (LSCs) that generate through aberrant differentiation the blast cells that make up the bulk of the malignant clone. LSCs were first identified as rare cells with an immunophenotype shared with normal hematopoietic stem cells. However, refinements of xenotransplantation assays, alternative methods of quantitation and syngeneic murine models have all led to an appreciation that LSCs display marked variability in frequency, immunophenotype and differentiation potential, both between and even within leukemias. [Oncogene] Abstract

Visit our reviews page to see a complete list of reviews in the cancer stem cell research field.  
 
INDUSTRY NEWS
Pediatric Oncologist Receives Grant for Neuroblastoma Research
Baylor College of Medicine and Texas Children’s Cancer Center pediatric oncologist Dr. Jason Shohet has received a grant from Braden’s Hope for Childhood Cancer to support his research to find novel treatments for high-risk neuroblastoma. This project targets neuroblastoma cells that have cancer stem cell characteristics, including the ability to divide and reproduce. [Baylor College of Medicine] Press Release

Cellectis Group Announces Groundbreaking In Vivo Proof of Concept Testing of Their Flagship UCART19 Product for Curative Therapy of Leukemia
Cellectis announced the successful in vivo proof of concept testing of their flagship UCART19 product for curative therapy of leukemia. UCART19 is a revolutionary engineered T-cell product that leverages Cellectis’ core technologies in genome engineering. [Cellectis] Press Release

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POLICY NEWS
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)  
 
EVENTS
NEW World Stem Cell Summit 2013
December 4-6, 2013
San Diego, United States

Visit our events page to see a complete list of events in the cancer stem cell community.
 
JOB OPPORTUNITIES
NEW Postdoctoral Fellow – Signal Transduction, Cancer Metabolism and Cancer Stem Cells (City of Hope – Beckman Research Institute)

NEW Postdoctoral Researcher – Molecular Bases of Cancer Initiation and Progression (New York University School of Medicine)

Postdoctoral Fellow – Cancer Stem Cell Biology (McGill University)

Postdoctoral Position – Molecular and Cellular Oncology (VIB Department for Molecular Biomedical Research, University of Ghent)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

Postdoctoral Fellow – Cancer Biology and Stem Cell (University of Texas Health Science Center at Houston)

PhD Studentship Opportunity – Tumor-Initiating Melanoma Cells (University of East Anglia)


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