|Cancer Stem Cell News 6.06 February 15, 2017|
Scientists showed that VEGFA mediates stem cell actions in primary human ovarian cancer (OVCA) culture and OVCA lines via VEGFR2-dependent Src activation to upregulate Bmi1, tumor spheres, and ALDH1 activity. VEGFA stimulated sphere formation only in the ALDH1+ subpopulation and increased OVCA-initiating cells and tumor formation in vivo through Bmi1. [EMBO Mol Med]
The authors describe metabolically inert L-glucosamine-based L-GAELs that retain the cytotoxic effects of the D-GAELs including the ability to kill BT-474 breast cancer stem cells. [J Med Chem]
Although the existence of cancer stem cells in intestine tumors has been suggested, direct evidence has not been yet provided. Investigators showed, using the multicolor lineage-tracing method and mouse models of intestinal adenocarcinoma and adenoma that Bmi1- or Lgr5- positive tumorigenic cells clonally expanded in proliferating tumors. [Sci Rep]
This study was conducted to assess doublecortin-like kinase 1 (DCLK1) expression levels in pancreatic neuroendocrine tumor (PNET) tissues and to explore the roles of this molecule in clinical tissue from multiple PNET patients, cells, and tumor xenografts. Evidence revealed that human PNETs diffusely and robustly express the cancer stem cell marker DCLK1, which drives SLUG-mediated epithelial-mesenchymal transition (EMT). [Mol Cancer Res]
Since hepatocellular carcinoma mostly develops on a cirrhotic background, researchers sought to determine whether cancer stem cell-like epithelial cell adhesion molecule (EpCAM+) cells exist in patients with advanced cirrhosis. Both flow cytometry and immunohistochemistry showed that frequency of EpCAM+ cells in advanced cirrhosis was increased as compared to control. [Stem Cells Transl Med]
Through shRNA silencing of the Nfkb2 gene, the role of p100/p52 in 4T1 and N202.1A cell lines were assessed by nuclear factor-kappa B (NF-κB) reporter, invasion, tumorsphere and orthotopic transplantation assays. Knockdown of Nfkb2 led to opposing changes in NF-κB-dependent transcription. NF-κB activity was elevated in 4T1 cells and this resulted in increased motility, cancer stem cell activity and tumorigenicity in vivo. [Breast Cancer Res Treat]
Scientists evaluated the effects of curcumin on patient-derived glioblastoma stem cell (GSC) lines. They demonstrated a curcumin-induced dose-dependent decrease in GSC viability. Treatment with sub-toxic levels of curcumin significantly decreased GSC proliferation, sphere forming ability and colony forming potential. [BMC Cancer]
In an effort to develop a cell line with improved tumorigenicity, investigators derived a new cell line from Hepa1-6 cells through an in vivo passage in C57BL/6 mice. The resulting Dt81Hepa1-6 cell line showed enhanced tumorigenicity compared to Hepa1-6 with more frequent and more rapid tumor development in C57BL/6 mice. [PLoS One]
The role of CK2 signaling in brain tumor initiating cell (BTIC) function was examined. Researchers found that expression of CK2α was increased in CD133+ BTICs compared to CD133– cells within the same glioblastoma xenolines. [J Neurooncol]
To understand the role of AF1q in stem-like population, scientists examined stem-like cells derived from breast cells which dysregulated Wnt signaling pathway by alteration of AF1q expression. The effect of Wnt signaling pathway by AF1q on EMT marker expression, stem cell marker expression, and sphere formation was determined. [Biochem Biophys Res Commun]
Recent genomic studies have unveiled the complexity of tumor heterogeneity in glioblastoma and provide new insights into the genomic landscape of tumor cells that survive and initiate tumor recurrence. Resistant cells also co-opt developmental pathways and display stem-like properties; hence the authors propose to name them recurrence-initiating stem-like cancer cells. [J Clin Invest]
Researchers summarize the current understanding of many of the pathways and mechanisms that promote the survival of the chronic phase chronic myeloid leukemia leukemic stem cell (LSC) and how they can be a source of new gene coding mutations that impact in the clinic. They also review recent pre-clinical approaches that show promise to eradicate the LSC, and future challenges on the path to cure. [Blood]
Visit our reviews page to see a complete list of reviews in the cancer stem cell research field.
RCSI (Royal College of Surgeons in Ireland) and Almac Discovery have announced a major research collaboration that aims to gain a new understanding of how to target tumor cells that are resistant to cancer therapies and cause cancer to spread to other parts of the body. The project will explore the potential of a drug, based on initial research by RCSI’s Professor Tracy Robson and developed by Almac Discovery, which is currently undergoing a Phase I dose escalation trial for patients with solid tumors. [Almac Discovery]
OncoMed Pharmaceuticals, Inc. announced it has enrolled and dosed the first patient in a Phase Ib clinical trial of its anti-DLL4/VEGF bispecific antibody in combination with paclitaxel in patients with platinum-resistant ovarian cancer. [OncoMed Pharmaceuticals, Inc.]
The eldest son of Henrietta Lacks wants compensation from Johns Hopkins University and possibly others for the unauthorized use of her cells in research that led to decades of medical advances. The cells taken from the 31-year-old after she died of an aggressive form of cervical cancer in 1951 were the first to live outside the body in a glass tube. They were dubbed the HeLa cells and have become the most widely used human cells that exist in scientific research. [The Washington Post]
If research funders demand open-access publishing, will subscription journals acquiesce? An announcement today by the publisher of Science suggests they will — as long as that funder is as influential as the Bill & Melinda Gates Foundation. [Nature News]
A panel of US Patent and Trademark Office judges have determined that a series of patents granted for CRISPR-Cas9 gene editing to the Broad Institute of MIT and Harvard will stand. [Nature News]
Political upheaval threatens Turkey’s ambitious plans for research and development. [Nature News]
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