Cancer Stem Cell News Volume 8.43 | Nov 06 2019

TOP STORY

CD9 Identifies Pancreatic Cancer Stem Cells and Modulates Glutamine Metabolism to Fuel Tumor Growth

Scientists identified tetraspanin CD9 as a marker of pancreatic ductal adenocarcinoma tumor-initiating cells. CD9^high cells had increased organoid formation capability, and generated tumor grafts in vivo at limiting dilutions. [Nat Cell Biol] Abstract

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Lineage Tracing of Acute Myeloid Leukemia Reveals the Impact of Hypomethylating Agents on Chemoresistance Selection

DNA methyltransferase inhibitors suppressed the outgrowth of a pre-determined set of chemoresistant acute myeloid leukemia clones with stemness properties, instead favoring the expansion of rarer and unfit chemosensitive clones. [Nat Commun] Full Article

A CD133-Akt-Wnt Signaling Axis Drives Glioblastoma Brain Tumor-Initiating Cells

Using several patient-derived CD133^high and CD133^low glioblastomas, researchers described intrinsic differences in determinants of stemness, which they owed to a CD133-AKT-Wnt signaling axis in which CD133 functioned as a putative cell surface receptor for AKT-dependent Wnt activation. [Oncogene] Abstract

Nrf2-Induced Reductive Stress Favours Self-Renewal of Breast Cancer Stem-Like Cells via the FoxO3a-BMI-1 Axis

The authors found that manifestation of stemness in breast cancer stem-like cells was associated with an elevated production of reduced glutathione maintained by upregulation of glutamate cysteine ligase catalytic subunit and consequently, lowered reactive oxygen species levels. [Antioxid Redox Signal] Abstract

The Paracrine Induction of Prostate Cancer Progression by Caveolin-1

Scientists demonstrated that the presence of caveolin-1 in tumor-derived exosomes acted as a potent driver to induce cancer stem cell (CSC) phenotypes and epithelial-mesenchymal transition in prostate cancer undergoing neuroendocrine differentiation through NFκB signaling pathway. [Cell Death Dis] Full Article

Radiation Responses of 2D and 3D Glioblastoma Cells: A Novel, 3D-Specific Radioprotective Role of VEGF/Akt Signaling through Functional Activation of NHEJ

Responses of primary glioblastoma stem-like cells to radiation in combination with EGFR, VEGF and Akt inhibition were investigated in conventional 2D cultures and a 3D in vitro model of glioblastoma stem-like cells that recapitulated key glioblastoma stem-like cells clinical features. [Mol Cancer Ther] Abstract

The Metabolic Inhibitor CPI-613 Negates Treatment Enrichment of Ovarian Cancer Stem Cells

Researchers demonstrated that treatment with the metabolic inhibitor CPI-613 in vitro decreased CD133⁺ and CD117⁺ cell frequency relative to untreated ovarian cancer cells, with negligible impact on non-cancer stem cell viability. [Cancers] Full Article

The Protein Arginine Methyltransferases 1 and 5 Affect Myc Properties in Glioblastoma Stem Cells

Investigators showed that Myc/protein arginine methyltransferase (PRMT) 5 protein complex included PRMT1, in both HEK293T and glioblastoma stem cells. They demonstrated that Myc was both asymmetrically and symmetrically dimethylated by PRMT1 and PRMT5, respectively, and that these modifications differentially regulated its stability. [Sci Rep] Full Article

CCND1 Silencing Suppresses Liver Cancer Stem Cell Differentiation through Inhibiting Autophagy

The cyclin D1 (CCND1) mRNA level was examined by qRT-PCR. The protein levels of autophagy markers (Becin-1 and LC3II) were examined by western blot to evaluate autophagy level. CD₁₃₃ was used as a liver cancer stem cell marker and CD₁₃₃⁺ cell percentage in hepatocellular carcinoma cells was detected by flow cytometry. [Hum Cell] Abstract

Eukaryotic Initiation Factor 5B (eIF5B) Regulates Temozolomide-Mediated Apoptosis in Brain Tumor Stem Cells (BTSCs)

Scientists investigated a mechanism in patient-derived BTSCs. They showed that silencing eIF5B leaded to increased temozolomide sensitivity in two BTSC lines, BT25 and BT48. Depletion of eIF5B decreased levels of anti-apoptotic proteins in BT48 and sensitized these cells to temozolomide-induced activation of caspase-3, cleavage of PARP, and apoptosis. [Biochem Cell Biol] Abstract

Adenosine Depletion as a New Strategy to Decrease Glioblastoma Stem-Like Cells Aggressiveness

Adenosine depletion was performed using recombinant adenosine deaminase. Migration and invasion were measured by transwell and matrigel-coated transwell assay, respectively. HIF-2α-dependent cell migration/invasion decreased in glioblastoma stem-like cells treated with adenosine deaminase under hypoxia. [Cells] Full Article

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Circulating Biomarkers in Patients with Glioblastoma

The authors summarize the current literature on circulating biomarkers, namely circulating tumor cells, circulating tumor DNA and extracellular vesicles as potential non-invasively sampled biomarkers to manage the treatment of patients with glioblastoma. [Br J Cancer] Full Article

The Role of Nrf2 Signaling in Cancer Stem Cells: From Stemness and Self-Renewal to Tumorigenesis and Chemoresistance

Nuclear factor-erythroid 2-related factor 2 (NRF2) signaling protects malignant cells from ROS damage against tumor growth and chemoresistance. Scientists discuss the role of NRF2 in stemness, self-renewal ability, tumorigenesis and chemoresistance of cancer stem cells. [Life Sci] Abstract | Graphical Abstract

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Hillstream BioPharma Announces Collaboration with Ardena to Support QUATRAMER Manufacturing

Hillstream BioPharma, Inc. announced a collaboration with Ardena to secure manufacturing feasibility and capacity for Hillstream’s QUATRAMER portfolio. This includes HSB-1216, a potent cancer stem cell inhibitor with initial indications for small cell lung cancer. [Hillstream BioPharma, Inc.] Press Release

VBL Therapeutics Announces New IND for an Investigator-Sponsored Phase II Trial of VB-111 in Recurrent Glioblastoma

VBL Therapeutics announced that an investigational new drug (IND) application has received clearance from the US FDA. The IND is for a Phase II randomized, controlled, clinical trial of VB-111 in recurrent glioblastoma patients undergoing a second surgery. [VBL Therapeutics] Press Release

NexImmune Receives IND Clearance for Phase I/II Trial in Acute Myeloid Leukemia / Myelodysplastic Syndrome

NexImmune received Investigational New Drug (IND) clearance for the company’s first cellular therapy product. NEXI-001 is being developed for the treatment of acute myeloid leukemia or myelodysplastic syndrome patients with relapsed disease after an allogeneic hematopoietic cellular transplant. [NexImmune] Press Release

Autolus Therapeutics Receives FDA Orphan Drug Designation for AUTO1 for Treatment of Acute Lymphoblastic Leukemia

Autolus Therapeutics plc announced that the FDA has granted AUTO1 orphan drug designation for treatment of acute lymphoblastic leukemia patients. [Autolus Therapeutics plc] Press Release

Report Sketches Vision for UK Research After Brexit

An eagerly awaited external report, commissioned by the government, lays out research priorities and options if those relationships with Europe are severed. It calls for increased spending on R&D nationwide, a new research fellowship program, and larger chunks of money for universities to quickly target research opportunities. [ScienceInsider] Editorial

South Korea Clamps Down on Academics Attending ‘Weak’ Conferences

South Korea’s education ministry wants to stop academics from participating in conferences that it considers “weak” and of little academic value. The ministry announced on 17 October that it will require all universities to adopt measures to vet academics’ travel to overseas conferences so as to “prevent researchers from engaging in poor academic activities”. [Nature News] Editorial

Science Chief at NIH Drug Abuse Institute Resigned After Sexual Misconduct Probe

In August, Antonello Bonci, scientific director of the National Institute on Drug Abuse, resigned, and the agency’s director told employees in an email that Bonci would be running an addiction institute in Florida. Science has learned that Bonci’s departure followed an investigation spurred by an internal complaint, which alleged that he sexually targeted a trainee and later directed resources to another trainee with whom he was in an intimate relationship. [ScienceInsider] Editorial

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