Cancer Stem Cell News Volume 6.06 | Feb 15 2017

TOP STORY

VEGFA Activates an Epigenetic Pathway Upregulating Ovarian Cancer-Initiating Cells

Scientists showed that VEGFA mediates stem cell actions in primary human ovarian cancer (OVCA) culture and OVCA lines via VEGFR2-dependent Src activation to upregulate Bmi1, tumor spheres, and ALDH1 activity. VEGFA stimulated sphere formation only in the ALDH1⁺ subpopulation and increased OVCA-initiating cells and tumor formation in vivo through Bmi1. [EMBO Mol Med] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Replacing D-Glucosamine with Its L-Enantiomer in Glycosylated Antitumor Ether Lipids (GAELs) Retains Cytotoxic Effects against Epithelial Cancer Cells and Cancer Stem Cells

The authors describe metabolically inert L-glucosamine-based L-GAELs that retain the cytotoxic effects of the D-GAELs including the ability to kill BT-474 breast cancer stem cells. [J Med Chem] Abstract

Intestinal Cancer Stem Cells Marked by Bmi1 or Lgr5 Expression Contribute to Tumor Propagation via Clonal Expansion

Although the existence of cancer stem cells in intestine tumors has been suggested, direct evidence has not been yet provided. Investigators showed, using the multicolor lineage-tracing method and mouse models of intestinal adenocarcinoma and adenoma that Bmi1- or Lgr5- positive tumorigenic cells clonally expanded in proliferating tumors. [Sci Rep] Full Article

Pancreatic Neuroendocrine Tumors and EMT Behavior Are Driven by the CSC Marker DCLK1

This study was conducted to assess doublecortin-like kinase 1 (DCLK1) expression levels in pancreatic neuroendocrine tumor (PNET) tissues and to explore the roles of this molecule in clinical tissue from multiple PNET patients, cells, and tumor xenografts. Evidence revealed that human PNETs diffusely and robustly express the cancer stem cell marker DCLK1, which drives SLUG-mediated epithelial-mesenchymal transition (EMT). [Mol Cancer Res] Abstract

EpCAM⁺ Liver Cancer Stem-Like Cells Exhibiting Autocrine Wnt Signaling Potentially Originate in Cirrhotic Patients

Since hepatocellular carcinoma mostly develops on a cirrhotic background, researchers sought to determine whether cancer stem cell-like epithelial cell adhesion molecule (EpCAM⁺) cells exist in patients with advanced cirrhosis. Both flow cytometry and immunohistochemistry showed that frequency of EpCAM⁺ cells in advanced cirrhosis was increased as compared to control. [Stem Cells Transl Med] Abstract | Full Article

Opposing Roles of Nfkb2 Gene Products p100 and p52 in the Regulation of Breast Cancer Stem Cells

Through shRNA silencing of the Nfkb2 gene, the role of p100/p52 in 4T1 and N202.1A cell lines were assessed by nuclear factor-kappa B (NF-κB) reporter, invasion, tumorsphere and orthotopic transplantation assays. Knockdown of Nfkb2 led to opposing changes in NF-κB-dependent transcription. NF-κB activity was elevated in 4T1 cells and this resulted in increased motility, cancer stem cell activity and tumorigenicity in vivo. [Breast Cancer Res Treat] Abstract

Curcumin Decreases Malignant Characteristics of Glioblastoma Stem Cells via Induction of Reactive Oxygen Species

Scientists evaluated the effects of curcumin on patient-derived glioblastoma stem cell (GSC) lines. They demonstrated a curcumin-induced dose-dependent decrease in GSC viability. Treatment with sub-toxic levels of curcumin significantly decreased GSC proliferation, sphere forming ability and colony forming potential. [BMC Cancer] Full Article

Highly Tumorigenic Hepatocellular Carcinoma Cell Line with Cancer Stem Cell-Like Properties

In an effort to develop a cell line with improved tumorigenicity, investigators derived a new cell line from Hepa1-6 cells through an in vivo passage in C57BL/6 mice. The resulting Dt81Hepa1-6 cell line showed enhanced tumorigenicity compared to Hepa1-6 with more frequent and more rapid tumor development in C57BL/6 mice. [PLoS One] Full Article

Protein Kinase CK2 Is Important for the Function of Glioblastoma Brain Tumor Initiating Cells

The role of CK2 signaling in brain tumor initiating cell (BTIC) function was examined. Researchers found that expression of CK2α was increased in CD133⁺ BTICs compared to CD133^– cells within the same glioblastoma xenolines. [J Neurooncol] Abstract

Activation of Wnt Signaling Pathway by AF1q Enriches Stem-Like Population and Enhance Mammosphere Formation of Breast Cells

To understand the role of AF1q in stem-like population, scientists examined stem-like cells derived from breast cells which dysregulated Wnt signaling pathway by alteration of AF1q expression. The effect of Wnt signaling pathway by AF1q on EMT marker expression, stem cell marker expression, and sphere formation was determined. [Biochem Biophys Res Commun] Abstract

Overcoming Therapeutic Resistance in Glioblastoma: The Way Forward

Recent genomic studies have unveiled the complexity of tumor heterogeneity in glioblastoma and provide new insights into the genomic landscape of tumor cells that survive and initiate tumor recurrence. Resistant cells also co-opt developmental pathways and display stem-like properties; hence the authors propose to name them recurrence-initiating stem-like cancer cells. [J Clin Invest] Abstract

The Chronic Myeloid Leukemia Stem Cell: Stemming the Tide of Persistence

Researchers summarize the current understanding of many of the pathways and mechanisms that promote the survival of the chronic phase chronic myeloid leukemia leukemic stem cell (LSC) and how they can be a source of new gene coding mutations that impact in the clinic. They also review recent pre-clinical approaches that show promise to eradicate the LSC, and future challenges on the path to cure. [Blood] Abstract

Visit our reviews page to see a complete list of reviews in the cancer stem cell research field.

RCSI and Almac Discovery Enter Research Collaboration to Target Therapy-Resistant Cancer Tumors

RCSI (Royal College of Surgeons in Ireland) and Almac Discovery have announced a major research collaboration that aims to gain a new understanding of how to target tumor cells that are resistant to cancer therapies and cause cancer to spread to other parts of the body. The project will explore the potential of a drug, based on initial research by RCSI’s Professor Tracy Robson and developed by Almac Discovery, which is currently undergoing a Phase I dose escalation trial for patients with solid tumors. [Almac Discovery] Press Release

OncoMed Enrolls First Patient in Phase Ib Clinical Trial of Its Anti-DLL4/VEGF Bispecific Antibody in Patients with Platinum-Resistant Ovarian Cancer

OncoMed Pharmaceuticals, Inc. announced it has enrolled and dosed the first patient in a Phase Ib clinical trial of its anti-DLL4/VEGF bispecific antibody in combination with paclitaxel in patients with platinum-resistant ovarian cancer. [OncoMed Pharmaceuticals, Inc.] Press Release

Henrietta Lacks’s Family Wants Compensation for Her Cells

The eldest son of Henrietta Lacks wants compensation from Johns Hopkins University and possibly others for the unauthorized use of her cells in research that led to decades of medical advances. The cells taken from the 31-year-old after she died of an aggressive form of cervical cancer in 1951 were the first to live outside the body in a glass tube. They were dubbed the HeLa cells and have become the most widely used human cells that exist in scientific research. [The Washington Post] Editorial

Science Journals Permit Open-Access Publishing for Gates Foundation Scholars

If research funders demand open-access publishing, will subscription journals acquiesce? An announcement today by the publisher of Science suggests they will — as long as that funder is as influential as the Bill & Melinda Gates Foundation. [Nature News] Editorial

Broad Institute Wins Bitter Battle over CRISPR Patents

A panel of US Patent and Trademark Office judges have determined that a series of patents granted for CRISPR-Cas9 gene editing to the Broad Institute of MIT and Harvard will stand. [Nature News] Editorial

The Turkish Paradox: Can Scientists Thrive in a State of Emergency?

Political upheaval threatens Turkey’s ambitious plans for research and development. [Nature News] Editorial

NEW Stem Cell Summit
April 26-28, 2017
Boston, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Position – Stem Cell and Cancer Biology (Lund University)

Postdoctoral Research Fellow Positions – Biomedical Research (Cincinnati Children’s Hospital Medical Center)

Postdoctoral Fellow – Cancer Stem Cells (Boston Children’s Hospital/Harvard Medical School)

Principal Investigator – Cancer Research and Oncology Drug Discovery (Southern Research Institute)

Research Fellow – Cancer and Stem Cell Biology (National University of Singapore)

Principal Scientist – Oncology (Janssen)

Postdoctoral Research – Cancer Genetics and Epigenetics (Fred Hutchinson Cancer Research Center)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Postdoctoral Fellow – Cancer Immunotherapy (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Viruses and Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Cancer Genetics/Epigenetics (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Cell Cycle Control and Tumorigenesis (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Ubiquitin System and Cancer (Fred Hutchinson Cancer Research Center)

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