Cancer Stem Cell News Volume 4.04 | Feb 4 2015

SOX9 Inhibits β-TrCP-Mediated Protein Degradation to Promote Nuclear GLI1 Expression and Cancer Stem Cell Properties
The High Mobility Group box protein SOX9 and the GLI1 transcription factor play protumorigenic roles in pancreatic ductal adenocarcinoma (PDA). Researchers observed positive feedback, such that SOX9-deficient PDA cells have severely repressed levels of endogenous GLI1, attributed to loss of GLI1 protein stability. [J Cell Sci] Abstract

ADAM-9 Is a Novel Mediator of Tenascin-C-Stimulated Invasiveness of Brain Tumor-Initiating Cells
Tenascin-C (TNC), an extracellular matrix protein overexpressed in malignant gliomas, stimulates invasion of conventional glioma cell lines. Researchers addressed whether and how TNC may regulate the invasiveness of brain tumor-initiating cells that give rise to glioma progenies. [Neuro Oncol] Abstract

TGF-β1 Acts through miR-155 to Down-Regulate TP53INP1 in Promoting Epithelial-Mesenchymal Transition and Cancer Stem Cell Phenotypes
Researchers report that miR-155 regulates not only the epithelial-mesenchymal transition but also the stem-like transition in liver cancer cells. Up-regulated miR-155 significantly increases the population of stem-like cancer stem cells among liver cancer cells and the ability to form tumor spheres. [Cancer Lett] Abstract

The Telomerase Inhibitor Imetelstat Alone, and in Combination with Trastuzumab, Decreases the Cancer Stem Cell Population and Self-Renewal of HER2⁺ Breast Cancer Cells
The authors investigated the effects of a telomerase antagonistic oligonucleotide, imetelstat, on cancer stem cell (CSC) and non-CSC populations of HER2⁺ breast cancer cell lines. Imetelstat alone and in combination with trastuzumab reduced the CSC fraction and inhibited CSC functional ability, as shown by decreased mammosphere counts and invasive potential. [Breast Cancer Res Treat] Abstract

A Critical Dose of Doxorubicin Is Required to Alter the Gene Expression Profiles in MCF-7 Cells Acquiring Multidrug Resistance
Investigators studied gene expression profiling circumstances in MCF-7 during multidrug resistance development. MCF-7/ADR-1024 cells exerted CSC-like cell surface marker CD44 high/CD24 low and form mammospheres. [PLoS One] Full Article

Antisense Inhibition of MicroRNA-21 and MicroRNA-221 in Tumor-Initiating Stem-Like Cells Modulates Tumorigenesis, Metastasis, and Chemotherapy Resistance in Pancreatic Cancer
Researchers identified a small population side population (SP) cells in pancreatic cancer cells with stem cell-like properties, which were able to induce fast and aggressive tumor formation in nude mice. Sorted SP cells from gemcitabine-resistant highly metastatic human pancreatic cancer cell line cells were orthotopically implanted in nude mice with or without miRNA-21 and miRNA-221 antisense oligonucleotides mono- and combination therapy. [Target Oncol] Abstract

Adoptive T-Cell Therapy of Prostate Cancer Targeting the Cancer Stem Cell Antigen EpCAM
Because cancer stem cells (CSCs) play an important role in tumor growth and metastasis, scientists hypothesized that adoptive transfer of T cells targeting a CSC antigen could result in dramatic anti-tumor effects. An EpCAM-specific chimeric antigen receptor was constructed to transduce human peripheral blood lymphocytes and thereby enable them to target the CSC marker EpCAM. [BMC Immunol] Full Article

p53 Upregulated Modulator of Apoptosis Sensitizes Drug-Resistant U251 Glioblastoma Stem Cells to Temozolomide through Enhanced Apoptosis
A temozolomide (TMZ)-resistant glioblastoma cell line, U251R, was developed and subsequently divided into two subpopulations according to the CD133 immunophenotype. TMZ achieves its cytotoxic effect by inducing DNA lesions and p53 upregulated modulator of apoptosis is an essential mediator of DNA damage-induced apoptosis independently of p53 status. [Mol Med Rep] Abstract | Download Full Article

Molecular Pathways: Novel Approaches for Improved Therapeutic Targeting of Hedgehog Signaling in Cancer Stem Cells
The authors discuss Hedgehog (Hh) signaling mechanisms in the context of human cancer, particularly in the maintenance of the cancer stem cell phenotype, and consider new therapeutic strategies that hold the potential to expand considerably the scope and therapeutic efficacy of Hh-directed anticancer therapy. [Clin Cancer Res] Abstract

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Stemline Therapeutics Announces SL-701 Granted Orphan Drug Designation for the Treatment of Glioma
Stemline Therapeutics, Inc announced that SL-701 has received orphan drug designation from the U.S. Food and Drug Administration for the treatment of glioma. A multicenter Phase II clinical trial is currently evaluating the anti-tumor activity of SL-701 in adult patients with second-line glioblastoma multiforme. [Stemline Therapeutics, Inc.] Press Release

Irving L. Weissman and Joan Massagué Win Charles Rodolphe Brupbacher Prize for Cancer Research
Researchers Irving L. Weissman and Joan Massagué have won this year’s Charles Rodolphe Brupbacher Prize for Cancer Research: Weissman, from Stanford University, for his work on healthy and sick stem cells; Massagué, from Memorial Sloan Kettering Cancer Center in New York, for his research on metastatic spread. [University of Zurich] Press Release

Cord Blood Registry Announces Formation of Scientific & Medical Advisory Board
Cord Blood Registry^® (CBR^®) announced the establishment of a Scientific and Medical Advisory Board (SMAB). Composed of internationally renowned stem cell experts, the SMAB will provide input and guidance to help advance CBR’s mission to expand the scope of newborn stem cell therapies that may be available to patients and their families. [Cord Blood Registry^®] Press Release

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NEW Director – Vector Production (Sangamo BioSciences, Inc.)

NEW Senior Process Development Engineer (Sangamo BioSciences, Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Junior Group Leaders – Cell Biology of Cancer and Genomic Instability (Foundation FIRC Institute of Molecular Oncology)

Postdoctoral Position – Stem Cell Biology/Cancer Biology (Oregon Health & Science University)

Postdoctoral Positions – Cancer Bioengineering and Cancer Biology (University of Minnesota)

Postdoctoral Fellow – Wnt Signaling in Development and Disease (Van Andel Research Institute)

Postdoctoral Research Fellow – Post-Transcriptional Gene Regulation Governing Cancer Cell Behavior (Fred Hutchinson Cancer Research Center)

Postdoctoral Positions – Functional Genomics of Stem Cells and Cancer (UT Southwestern Medical Center)

Postdoctoral Fellow – Stem Cells and Cancer (Tsinghua University)

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