|Cancer Stem Cell News 6.00 January 4, 2017|
Researchers have discovered a metabolic signature critical for the functioning of “cancer stem cells” that initiate tumor formation. The team also showed how to interfere with this metabolic mechanism in ovarian cancer, inhibiting tumor growth. [Press release from Purdue University discussing online prepublication in Cell Stem Cell]
Investigators implemented a novel chemoresistant prostate cancer patient-derived xenograft model in NOD/SCID mice and identified CD54 as a candidate gene among the most highly enriched gene expression profiles in prostate tumors exposed to chronic cisplatin administration. [Theranostics]
PARP inhibitors have shown promising results in early studies for treatment of breast cancer susceptibility gene (BRCA)–deficient breast cancers; however, resistance ultimately develops. The authors demonstrated that the cancer stem cells in BRCA1-mutant triple-negative breast cancers were resistant to PARP inhibition, and that these cells had both elevated RAD51 protein levels and activity. [Clin Cancer Res]
The CXCR4 chemokine and sonic hedgehog (SHH) morphogen pathways are validated therapeutic targets in many cancer types, including medulloblastoma. Researchers showed that dual inhibition of the SHH and CXCR4 pathways exerted potent antitumor effects in a murine model of SHH-subtype medulloblastoma. [Cancer Res]
Brain invasion by glioblastoma (GBM) determines prognosis, recurrence and lethality in patients, but no master factor coordinating the invasive properties of GBM has been identified. Investigators reported evidence favoring such a role for the non-canonical WNT family member Wnt5a. [Cancer Res]
The authors showed that RE1 silencing transcriptional factor (REST) represses 2 major miR gene targets in high-REST-glioblastoma stem-like cells: miR-203, a new target, and miR-124, a known target. They further showed that while miR-124 and the REST-miR-124 pathways regulate self-renewal, apoptosis and invasion, miR-203 and the REST-miR-203 pathways regulate only invasion. [Neuro Oncol]
Using stem-like sphere-forming cells prepared from a mammary tumor and a lung adenocarcinoma cell line, scientists found that CD59 was upregulated to protect cancer stem cells (CSCs) from complement-dependent cytotoxicity. Furthermore, they identified that SOX2 upregulates CD59 in epithelial CSCs. [Stem Cell Reports]
Researchers characterized cancer stem cells (CSCs) in primary hepatocellular carcinoma (HCC) and identified CD133 as a CSC surface marker. CD133+ HCC cells displayed more stem cell-like properties, tumor spheroid-forming ability, chemoresistance, migration ability, and tumorigenic capacity than CD133– HCC cells. [Cancer Lett]
The authors recently reported that the polycomb complex protein Bmi1 is a marker for lingual epithelial stem cells, which are involved in the long-term maintenance of lingual epithelial tissue in the physiological state. Using a mouse model of chemically induced tongue cancer and the multicolor lineage tracing method, they found that each unit of the tumor was generated by a single cell and that the assembly of such cells formed a polyclonal tumor. [Sci Rep]
Researchers previously reported that autocrine TNF-α (TNF) is responsible for JNK pathway activation in a subset of acute myeloid leukemia (AML) patient samples, providing a survival/proliferation signaling parallel to NF-κB in AML stem cells. In this study, they reported that most TNF-expressing AML cells also express another pro-inflammatory cytokine, IL1β, which acts in a parallel manner. [Oncotarget]
Investigators systematically examined the role of telomerase activity in lung and ovarian cancer stem cell propagation. More specifically, they showed that the cancer cells with higher telomerase activity are more energetically activated, with increased mitochondrial mass and function, as well as increased glycolytic activity. [Oncotarget]
Scientists investigated whether SDF-1α is a niche factor that through its interactions with CXCR4 and/or its second receptor CXCR7 on glioma stem-like cells (GSLCs) facilitates their homing to niches. Furthermore, they aimed to prove that SDF-1α cleavage by CatK inactivates SDF-1α and inhibits the invasion of GSLCs. [Biochim Biophys Acta]
The goal of this study was to clarify the functional significance of aldehyde dehydrogenase (ALDH) enzymatic activity on thyroid cancer stem cells properties in anaplastic thyroid cancer cell lines. Investigators found that N,N-diethylaminobenzaldehyde almost completely suppressed ALDH activity without affecting cell proliferation or spherogenicity. In contrast, an ALDH2 inhibitor disulfiram inhibited spherogenicity but did not inhibit ALDH1A3 activity. [Endocrine]
This review compiles information about different methods of detection and dissociation, side population, cellular markers and establishment culture of cancer stem cells (CSCs), as well as characteristics of CSCs such as tumorigenicity, and signaling pathways associated with self-renewal and the capability of the same histological tumor regeneration in various cancers. [J Cell Physiol]
Visit our reviews page to see a complete list of reviews in the cancer stem cell research field.
NewVac LLC reported meeting all primary endpoints in the Phase II Clinical Trial of quisinostat which NewVac licensed from Janssen Pharmaceutica NV. The clinical trial is evaluating the efficacy and safety of Quisinostat in Platinum-Resistant Ovarian Cancer in combination with Paclitaxel and Carboplatin. [NewVac LLC]
Tarveda Therapeutics, Inc. announced that a Phase I/IIa clinical trial evaluating PEN-221 in patients with advanced neuroendocrine tumors and small cell lung cancer expressing the somatostatin receptor 2 is underway, with patients enrolled and treated. [Tarveda Therapeutics, Inc.]
Lycera Corp. announced the initiation of a Phase I/IIa clinical trial of the company’s novel immuno-oncology therapeutic candidate LYC-55716, in patients with advanced, relapsed, or refractory solid tumors. [Lycera Corp.]
House Republicans conclude that tissue from aborted fetuses is of limited value for research and seek to reduce funding. [Nature News]
Hundreds of young researchers occupied Argentina’s science ministry in Buenos Aires last month, angry at budget cuts that they say have denied them permanent jobs at the country’s National Scientific and Technical Research Council. The occupation was the most extreme action yet by Argentinian scientists after months of protests at last year’s budget, the first under President Mauricio Macri. And the occupation seems to have paid off, in part: many of those involved have been offered extensions to their fellowships. [Nature News]
NEW Keystone Symposium: Tumor Metabolism: Mechanisms and Targets
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