Volume 2.09 | Mar 6

Cancer Stem Cell News 2.09 March 6, 2013
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TOP STORY
Ovarian Surface Epithelium at the Junction Area Contains a Cancer-Prone Stem Cell Niche
Investigators identified the hilum region of the mouse ovary, the transitional (or junction) area between the ovarian surface epithelium (OSE), mesothelium and tubal (oviductal) epithelium, as a previously unrecognized stem cell niche of the OSE. The hilum cells show increased transformation potential after inactivation of tumor suppressor genes Trp53 and Rb1, whose pathways are altered frequently in the most aggressive and common type of human epithelial ovarian cancer (EOC), high-grade serous adenocarcinoma. This study supports experimentally the idea that susceptibility of transitional zones to malignant transformation may be explained by the presence of stem cell niches in those areas. [Nature] Abstract | Press Release

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PUBLICATIONS (Ranked by impact factor of the journal)

Loss of FBP1 by Snail-Mediated Repression Provides Metabolic Advantages in Basal-Like Breast Cancer
Researchers showed that the Snail-G9a-Dnmt1 complex, which is critical for E-cadherin promoter silencing, is also required for the promoter methylation of fructose-1,6-biphosphatase (FBP1) in basal-like breast cancer. Loss of FBP1 also inhibits oxygen consumption and reactive oxygen species production by suppressing mitochondrial complex I activity; this metabolic reprogramming results in an increased cancer stem cell-like property and tumorigenicity by enhancing the interaction of β-catenin with T-cell factor. [Cancer Cell]
Abstract | Press Release

Selective Requirement of PI3K/PDK1 Signaling for Kras Oncogene-Driven Pancreatic Cell Plasticity and Cancer
Scientists showed that cell-autonomous phosphoinositide 3-kinase (PI3K) and 3-phosphoinositide-dependent protein kinase 1 (PDK1), but not Craf, are key effectors of oncogenic Kras in the pancreas, mediating cell plasticity, acinar-to-ductal metaplasia, and pancreatic ductal adenocarcinoma formation. [Cancer Cell] Abstract

Systemic Delivery of MicroRNA-34a for Cancer Stem Cell Therapy
A solid lipid nanoparticle (SLN) system was developed to deliver microRNA-34a (miR-34a) relevant for cancer stem cell therapy into lung tissues. In miR-34a-containing SLNs, miR-34a is protected from degradation in the serum and its cellular-transfection efficiency in vitro is increased. [Angew Chem Int Ed Engl] Abstract

Side Population in Human Glioblastoma Is Non-Tumorigenic and Characterizes Brain Endothelial Cells
The identification and significance of cancer stem-like cells in malignant gliomas remains controversial. It has been proposed that cancer stem-like cells display increased drug resistance, through the expression of ATP-binding cassette transporters that detoxify cells by effluxing exogenous compounds. Researchers investigated the ‘side population’ phenotype based on efflux properties of ATP-binding cassette transporters in freshly isolated human glioblastoma samples and intracranial xenografts derived thereof. [Brain]
Full Article

Notch Pathway Activity Identifies Cells with Cancer Stem Cell-Like Properties and Correlates with Worse Survival in Lung Adenocarcinoma
The authors aimed to determine the role of Notch activity in identifying lung cancer stem cells. They investigated the role of Notch activity in lung adenocarcinoma utilizing a Notch GFP-reporter construct and a gamma-secretase inhibitor, which inhibits Notch pathway activity. [Clin Cancer Res] Abstract

MiR203 Mediates Subversion of Stem Cell Properties during Mammary Epithelial Differentiation via Repression of ΔNP63α and Promotes Mesenchymal-to-Epithelial Transition
ΔNp63α, the predominant TP63 isoform in mammary epithelia, is robustly expressed in mammary stem cells (MaSCs) and is required for preservation of self-renewing capacity in diverse epithelial structures. These studies support a model in which induction of microRNA-203 (miR203) mediates forfeiture of self-renewing capacity via suppression of ΔNp63α and may also have anti-tumorigenic activity through its reduction of epithelial-to-mesenchymal transition and cancer stem cell populations. [Cell Death Dis] Full Article

Marked Improvement of Cytotoxic Effects Induced by Docetaxel on Highly Metastatic and Androgen-Independent Prostate Cancer Cells by Downregulating Macrophage Inhibitory Cytokine-1
The downregulation of macrophage inhibitory cytokine-1 (MIC-1) in LNCaP-LN3 and PC3M-LN4 cells significantly decreased their invasive capacity and promoted the antiproliferative, anti-invasive and mitochondrial- and caspase-dependent apoptotic effects induced by docetaxel. The downregulation of MIC-1 in PC3M-LN4 cells was also effective in promoting the cytotoxic effects induced by docetaxel on the side population (SP) endowed with stem cell-like properties and the non-SP cell fraction from PC3M-LN4 cells. [Br J Cancer] Abstract

Cancer Stem-Like Cell Properties Are Regulated by EGFR/AKT/β-Catenin Signaling and Preferentially Inhibited by Gefitinib in Nasopharyngeal Carcinoma
Investigators reported that the EGFR pathway plays a critical role in regulating cancer stem-like cells (CSCs) in nasopharyngeal carcinoma. Effects of EGFR on maintaining CSCs are mainly mediated by AKT signaling, and β-catenin is responsible for governing CSC properties in response to EGFR/AKT activation. [FEBS J] Abstract

Methyl Antcinate A Suppresses the Population of Cancer Stem-Like Cells in MCF7 Human Breast Cancer Cell Line
The authors examined the effect of methyl antcinate A on cancer stem-like cells in the MCF7 human breast cancer cell line. [Molecules] Abstract | Full Article

Culture Human Glioma-Derived Tumorspheres with NeuroCult™ - View Publications

REVIEWS
MicroRNAs Regulate Both Epithelial-to-Mesenchymal Transition and Cancer Stem Cells
The molecular determinants underlying the plasticity of cancers are currently the object of extensive research efforts, and a substantial body of evidence suggests that these models can be connected by the regulatory role of microRNAs, small noncoding RNA molecules with a fundamental role in many cellular functions. This review highlights and discusses this link and its possible implications for the fight against cancer. [Oncogene] Abstract
INDUSTRY NEWS

ImmunoCellular Therapeutics Announces Issuance of Key Patent for ICT-121 Cancer Vaccine
ImmunoCellular Therapeutics, Ltd. announced that the US Patent and Trademark Office has issued a key patent application covering ICT-121, an immunotherapeutic vaccine targeting CD133, an important cancer stem cell marker that is commonly overexpressed on a broad range of solid tumors. The patent includes claims covering composition of matter as well as methods of use. [Business Wire] Press Release

Advanced Cell Diagnostics Initiates Agreement to Study Biomarkers for Cancer Immunotherapy
Advanced Cell Diagnostics, Inc. (ACD) announced that they have entered into an agreement with The Johns Hopkins University on behalf of its Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins to use ACD’s proprietary RNAscope® technology platform to validate novel biomarkers and drug targets for cancer immunotherapy. [Advanced Cell Diagnostics, Inc.] Press Release

Quest for Cures: The Leukemia & Lymphoma Society Seeks to Fund Three Critical Areas of Blood Cancer Research
Medical innovation and sustained research investment are dramatically transforming the landscape in blood cancers. To that end, The Leukemia & Lymphoma Society (LLS) continues to drive a progressive research agenda to improve outcomes for patients who urgently need new therapies. LLS announced it has identified three priority areas toward which it will direct new funding. [The Leukemia & Lymphoma Society]
Press Release

 
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 Cancer Immunotherapy (CIMT) Annual Meeting 2013
May 14-16, 2013
Mainz, Germany

Visit
our events page to see a complete list of events in the cancer stem cell community.
JOB OPPORTUNITIES

Faculties in Cancer Biology & Immunotherapy (Huzhou University School of Medicine)

Postdoctoral Scientist (Eli Lilly)

Postdoctoral Position (University of Kentucky College of Medicine)

PhD Studentship Opportunity (University of East Anglia)

Postdoctoral Fellow – Epigenetics (Structural Genomics Consortium at University of Toronto)

Postdoctoral Fellowship – Hematopoietic and Leukemia Stem Cells (Cincinnati Children’s Hospital and Medical Center)

PhD Student (Universitätsklinikum Carl Gustav Carus)

PhD Studentship – Signal Transduction and Cancer Research (Department of Medicine, McGill University)


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