Cancer Stem Cell News Volume 2.27 | Jul 10 2013

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

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

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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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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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