Cancer Stem Cell News Volume 8.28 | Jul 24 2019

TOP STORY

Absence of NKG2D Ligands Defines Leukemia Stem Cells and Mediates Their Immune Evasion

Using xenografts of human acute myeloid leukemia (AML) as well as syngeneic mouse models of leukemia, researchers showed that ligands of the danger detector NKG2D — a critical mediator of anti-tumor immunity by cytotoxic lymphocytes, such as NK cells — were generally expressed on bulk AML cells but not on leukemic stem cells. [Nature] Abstract

(Ranked by impact factor of the journal)

LncRNA HAND2-AS1 Promotes Liver Cancer Stem Cell Self-Renewal via BMP Signaling

Human HAND2-AS1 and its mouse ortholog lncHand2 displayed a high level of conservation. HAND2-S1 was required for the self-renewal maintenance of liver CSCs to initiate hepatocellular carcinoma development. [EMBO J] Abstract | Graphical Abstract

Ovarian Cancer Stem Cells and Macrophages Reciprocally Interact through the WNT Pathway to Promote Pro-Tumoral and Malignant Phenotypes in 3D Engineered Microenvironments

To mimic a malignant ascites microenvironment, investigators created a hanging-drop hetero-spheroid model to bring CSCs and macrophages in close association. Within these hetero-spheroids, CD68⁺ macrophages made up ~20% of the population, while the rest were ovarian cancer cells and ovarian CSCs. [J Immunother Cancer] Full Article

SET Domain-Containing Protein 4 Epigenetically Controls Breast Cancer Stem Cell Quiescence

Upon activation, a SET domain-containing protein 4 (SETD4)-defined quiescent breast CSC (qBCSC) sustained itself in a quiescent state by asymmetric division, concurrently producing an active daughter cell that proliferated to produce a cancer cell population. Single-cell sequence analysis indicated that SETD4+qBCSCs clustered together as a distinct cell type within the heterogeneous BCSC population. [Cancer Res] Abstract

Humanized Anti-CD271 Monoclonal Antibody Exerts an Anti-Tumor Effect by Depleting Cancer Stem Cells

The authors established a humanized anti-CD271 monoclonal antibody (hCD271mAb). hCD271mAb bound to the cysteine-rich domain 1 of human CD271 with high affinity. In vitro, hCD271mAb exerted antibody-dependent cell-mediated cytotoxicity activity against SP2/0-CD271, ahuman CD271-transduced mouse cell line. [Cancer Lett] Abstract

Tcf7l1 Acts as a Suppressor for the Self-Renewal of Liver Cancer Stem Cells and Is Regulated by IGF/MEK/ERK Signaling Independent of β-Catenin

Mechanistically, Tcf7l1 regulated the self-renewal abilities of liver CSCs through transcriptional repression of the Nanog gene, and the effect was independent of β-catenin. Moreover, scientists found that Tcf7l1 expression was controlled by extracellular IGF signaling, and they demonstrated for the first time that IGF signaling stimulated Tcf7l1 phosphorylation and degradation through the MEK/ERK pathway. [Stem Cells] Abstract

Reversal of Sorafenib Resistance in Hepatocellular Carcinoma: Epigenetically Regulated Disruption of 14-3-3η/Hypoxia-Inducible Factor-1α

An analysis of the underlying molecular mechanisms revealed that 14-3-3η stabilized hypoxia-inducible factor 1α through the inhibition of ubiquitin-dependent proteasome protein degradation, which led to the maintenance of CSC properties. The authors further found that microRNA-16 was a competent miRNA that reversed sorafenib resistance by targeting the 3′-UTR of 14-3-3η and thereby inhibited 14-3-3η/HI-1α/CSC properties. [Cell Death Discov] Full Article

MicroRNA-95 Knockdown Inhibits Epithelial–Mesenchymal Transition and Cancer Stem Cell Phenotype in Gastric Cancer Cells through MAPK Pathway by Upregulating DUSP5

MiR-95 and DUSP5 expression was altered in a gastric cancer (GC) cell line to evaluate their respective effects on the epithelial-mesenchymal transition process, cellular processes, CSC phenotype, as well as tumor growth ability. It was further predicted in bioinformatic prediction and verified in GC tissue and cell line experiments that miR-95 was highly expressed in GC. [J Cell Physiol] Abstract

Simulated Microgravity Increases Polyploid Giant Cancer Cells and Nuclear Localization of YAP

Researchers described the role of simulation of microgravity (SMG) using a rotary cell culture system in increasing stemness in human colorectal cancer cell HCT116. They observed distinct features of cancer stem cells including CD133/CD44 dual positive cells and migration in SMG which was not altered by autophagy induction or inhibition. [Sci Rep] Full Article

Subscribe to one of our other 19 science newsletters such as Neural Cell News & Hematopoiesis News.

Neural Stem Cell Dynamics: The Development of Brain Tumours

Brain tumors are frequently characterized by a block in differentiation, implying that normal developmental pathways become hijacked during tumorigenesis. However, the heterogeneity of stem cells and their progenitors in the brain suggests there are many potential routes to tumor initiation. [Curr Opin Cell Biol] Abstract

Exploiting Metabolic Vulnerabilities for Personalized Therapy in Acute Myeloid Leukemia

The authors discuss the role of metabolic and mitochondrial pathways dysregulated in acute myeloid leukemia, and the potential of therapeutic intervention targeting these metabolic dependencies on proliferation, differentiation, stem cell function and cell survival to improve patient stratification and outcomes. [BMC Biol] Full Article

The Role of Cancer Stem Cells and Mechanical Forces in Ovarian Cancer Metastasis

Investigators highlight cancer stem cells’ roles in modulating ovarian cancer metastasis. Specifically, they outline the clinical relevance of cancer stem-like cells, and challenges associated with their identification and characterization and summarize the ways in which they modulate ovarian cancer metastasis. [Cancers] Full Article

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

Diffusion Pharmaceuticals Reports Favorable Safety Data for Dose-Escalation Run-In of Phase III INTACT Study in Glioblastoma Multiforme Patients

Diffusion Pharmaceuticals Inc. reported that based on favorable safety data in a 19-patient dose-escalation run-in study, the Data Safety Monitoring Board has recommended the continuation of the company’s Phase III clinical trial with trans sodium crocetinate in inoperable glioblastoma multiforme patients. [Diffusion Pharmaceuticals] Press Release

FDA Approves Pfizer’s Biosimilar, RUXIENCE™ (Rituximab-Pvvr), for Certain Cancers and Autoimmune Conditions

Pfizer Inc. announced the FDA has approved RUXIENCE™, a biosimilar to Rituxan^®, for the treatment of adult patients with non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and granulomatosis with polyangiitis and microscopic polyangiitis. [Pfizer Inc.] Press Release

Mustang Bio Receives Orphan Drug Designation for MB-102 (CD123 CAR T) for the Treatment of Acute Myeloid Leukemia

Mustang Bio, Inc. announced that the FDA has granted Orphan Drug Designation to MB-102 for the treatment of acute myeloid leukemia. [Mustang Bio, Inc.] Press Release

Fight for Coveted CRISPR Patents Gets Knottier, as MilliporeSigma Makes New Claims

After nearly seven years of failing to win fundamental patents on the genome-editing technology CRISPR, a unit of one of the world’s largest life sciences companies has thrown a Hail Mary: Late last Friday, MilliporeSigma petitioned the US Patent and Trademark office to open an interference proceeding between CRISPR-Cas9 patents that it applied for way back in 2012 and patents that the University of California has applied for or been awarded. [STAT News] Editorial

What Boris Johnson’s Leadership Could Mean for Science

Boris Johnson has been selected as the United Kingdom’s new prime minister — and is poised to lead the country out of the European Union. At the forefront of many scientists’ minds are questions about how Johnson’s leadership, including his support for a ‘no deal’ Brexit, will affect research. They fear that British science has much to lose from a messy departure from the EU. [Nature News] Editorial

NEW 48^th International Society for Experimental Hematology Annual Scientific Meeting
August 22-25, 2019
Brisbane, Australia

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

NEW Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Postdoctoral Associate – Hematopetic Stem Cells and Leukemia (The Jackson Laboratory)

Professor – Cancer and Stem Cell Immunology (University of Sherbrooke)

Postdoctoral Fellowship – Reprogramming Glioblastoma (Lund University)

Postdoctoral Research Position – B-Cell Acute Lymphoblastic Leukemia Research (University of California San Francisco)

Research Scientist – Leukemia Stem/Progenitor Cell Research (MD Anderson Cancer Center)

Postdoctoral Scientist – Cancer Organoids (Rutgers Cancer Institute of New Jersey)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Postdoctoral Fellow – Jak-Stat Signaling in Prostate & Pancreatic Cancer (Medical College of Wisconsin)

Tier I Canada Research Chair – Precision & Molecular Oncology (University of Calgary)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Cancer Stem Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.