|Cancer Stem Cell News 8.28 July 24, 2019|
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
Visit our reviews page to see a complete list of reviews in the cancer stem cell research field.
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]
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.]
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.]
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]
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]
NEW 48th International Society for Experimental Hematology Annual Scientific Meeting
Visit our events page to see a complete list of events in the community.
Have we missed an important article or publication in Cancer Stem Cell News? Click here to submit!
Comments or suggestions? Submit your feedback here.