|Cancer Stem Cell News 6.10 March 15, 2017|
Investigators showed through lineage tracing and genetic ablation that BMI1+ cancer stem cells (CSCs) mediate invasive growth and cervical lymph node metastasis in a mouse model of squamous cell carcinoma in the head and neck (HNSCC). This model and primary human HNSCC samples contain highly tumorigenic, invasive, and cisplatin-resistant BMI1+ CSCs, which exhibit increased AP-1 activity that drives invasive growth and metastasis of HNSCC. [Cell Stem Cell]
Scientists showed that dual targeting of epidermal growth factor receptor (EGFR) and Notch2/3 receptors with antibody CT16 not only inhibited signaling mediated by these receptors but also showed a strong anti–stem cell effect both in vitro and in vivo. [Sci Transl Med]
Acute myeloid leukemia (AML) cells differentially expressed serotonin receptor type 1 (HTR1) compared with healthy blood cells and the most primitive hematopoietic fraction; HTR1B expression on AML patient samples correlated with clinical outcome. Inhibition of HTR1s activated the apoptosis program, induced differentiation and reduced the clonogenic capacity, while minimal effect was observed on healthy blood cells. [Leukemia]
The authors found that the mitochondrial morphology of glioma stem‐like cells (GSCs) modulates the ER–mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER–mitochondria contacts compared to glioma differentiated cells. [EMBO J]
While it is clear that the tumor microenvironment (TME) contributes to cancer cell plasticity, the specific TME factors most actively controlling plasticity remain largely unknown. Researchers performed a screen to identify TME cytokines and growth factors that promote epithelial–mesenchymal plasticity, and acquisition of cancer stem cell properties. [Oncogene]
Stimulation of CD95/Fas drives and maintains cancer stem cells (CSCs). Scientists reported that this involves activation of signal transducer and activator of transcription 1 (STAT1) and induction of STAT1-regulated genes and that this process is inhibited by active caspases. STAT1 is enriched in CSCs in cancer cell lines, patient-derived human breast cancer, and CD95high-expressing glioblastoma neurospheres. [Cell Rep]
Cancer stem cells-enriched malignant mesothelioma cell subpopulations were identified by an OCT4/SOX2 reporter approach and were characterized by (1) increased resistance to cisplatin, (2) increased sensitivity toward the FAK inhibitor VS-6063 in vitro, and (3) a higher tumor-initiating capacity in vivo in orthotopic xenograft and allograft mouse models. [Stem Cell Reports]
To investigate common regulatory networks in both neural and glioblastoma stem cells, researchers subjected both cell types to in vitro differentiation conditions and measured global gene-expression changes using gene expression microarrays. [Sci Rep]
Treatment with CAT-SKL—a re-engineered protein form of the antioxidant enzyme catalase—inhibited cancer stem-like cells (CSCs), and treatment with the EGFR-specific small molecule kinase inhibitor erlotinib inhibited non-CSCs. Combining the antioxidant CAT-SKL with erlotinib targeted both CSCs and bulk cancer cells in cultures of EGFR-expressing triple-negative breast cancer-derived cells. The authors also report evidence that the mechanism for CAT-SKL inhibition of CSCs may depend on antioxidant-induced downregulation of a short alternative mRNA splicing variant of the methyl-CpG binding domain 2 gene, isoform MBD2c. [Sci Rep]
Investigators found family with sequence similarity 83, member A (FAM83A) is significantly overexpressed and associated with poorer overall survival and disease-free survival in pancreatic cancer. Overexpression of FAM83A markedly promoted, whereas inhibition of FAM83A decreased, cancer stem cells-like traits and chemoresistance both in vitro and in an in vivo mouse model of pancreatic cancer. [Oncogenesis]
Scientists aimed to explore the effect of Notch pathway on stemness of cancer stem cells in renal cell carcinoma and the underlying mechanisms. [J Exp Clin Cancer Res]
The authors review drugs targeting cancer stem-like cells, in selected epithelial cell-derived cancers. [Stem Cells]
Visit our reviews page to see a complete list of reviews in the cancer stem cell research field.
Boston Biomedical will present data from six preclinical studies – including five late-breaking posters – from its research and development portfolio. [Press release from Boston Biomedical discussing research to be presented at 2017 American Association for Cancer Research (AACR) Annual Meeting, Washington D.C.]
FDA Approves Merck’s KEYTRUDA® (Pembrolizumab) for Adult and Pediatric Patients with Classical Hodgkin Lymphoma (cHL) Refractory to Treatment, or who Have Relapsed after Three or More Prior Lines of Therapy
Merck announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA®, the company’s anti-programmed death receptor-1 therapy, for the treatment of adult and pediatric patients with refractory cHL, or who have relapsed after three or more prior lines of therapy. [Merck]
The US Food and Drug Administration (FDA) has approved Kisqali® in combination with an aromatase inhibitor as initial endocrine-based therapy for treatment of postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2) advanced or metastatic breast cancer. [Novartis]
Like a zombie that keeps on kicking, legal battles over mutant mice used for Alzheimer’s research are haunting the field once again — four years after the last round of lawsuits. In the latest case, the University of South Florida in Tampa has sued the US National Institutes of Health for authorizing the distribution of a particular type of mouse used in the field. [Nature News]
For months after the United Kingdom (U.K.) voted last June to leave the European Union (EU), many British scientists clung to hopes of a “soft Brexit,” which would not cut them off from EU funding and collaborators. But Prime Minister Theresa May, who is expected to trigger the two-year process of exiting the European Union, has signaled the break will be sharp. U.K. researchers are now facing up to the prospect that they won’t be able to apply for EU funding or easily recruit students and colleagues from the rest of Europe. [ScienceInsider]
A vote in Canada’s Parliament to approve a genetic privacy bill is creating a self-inflicted political headache for Prime Minister Justin Trudeau’s Liberal government—and could result in a relatively rare and unusual court case. [ScienceInsider]
President Donald Trump has nominated Scott Gottlieb — a conservative pundit, physician and venture capitalist — to head the US Food and Drug Administration (FDA). [Nature News]
NEW Metabolism in Time and Space: Emerging Links to Cellular and Developmental Programs
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Home Cancer Stem Cell News Volume 6.10 | Mar 15 2017