Cancer Stem Cell News Volume 2.40 | Oct 9 2013

Instruction of Hematopoietic Lineage Choices, Evolution of Transcriptional Landscapes and Cancer Stem Cell Hierarchies Derived from an AML1-ETO Mouse Model
AML1-ETO expression modified the lineage potential of hematopoietic stem cells, resulting in the selective expansion of the myeloid compartment at the expense of normal erythro- and lymphopoiesis. This lineage skewing was followed by a second substantial rewiring of transcriptional networks occurring in the trajectory to manifest leukemia. Researchers found that both HSC and lineage-restricted granulocyte macrophage progenitors acquired leukemic stem cell potential being capable of initiating and maintaining the disease. [EMBO Mol Med] Full Article

CD44 Expressed on CAFs Is a Functional Molecule Supporting the Stemness and Drug Resistance of Malignant Cancer Cells in the Tumor Microenvironment
Scientists showed that cancer-associated fibroblasts (CAFs) support tumor growth in vivo and maintain the stemness of cancer stem/initiating cells in an in vitro model using an established CAF cell line. [Stem Cells] Abstract

Inhibition of EGFR Induces a c-MET Driven Stem Cell Population in Glioblastoma
Investigators identified a distinct fraction of cells in a genetically engineered mouse model of EGFR-driven glioblastoma multiforme that respond to anti-EGFR therapy by inducing high levels of c-MET expression. [Stem Cells] Abstract

Cancer-Initiating Cells Derived from Human Rectal Adenocarcinoma Tissues Carry Mesenchymal Phenotypes and Resist Drug Therapies
Investigators identified rectal cancer-initiating cells (R-CICs) that possess differentiation potential in tumors derived from patients with rectal adenocarcinoma. The R-CICs carried both CD44 and CD54 surface markers, while R-CICs and their immediate progenies carried potential epithelial-mesenchymal transition characteristics. [Cell Death Dis] Full Article

Tumor Microenvironmental Signaling Elicits Epithelial-Mesenchymal Plasticity through Cooperation with Transforming Genetic Events
Investigators explored how extrinsic, tumor microenvironmental cytokines cooperate with intrinsic, genetic changes to promote epithelial-to-mesenchymal transition in human mammary epithelial cells (HMECs). Viral transduction of transforming genetic events into HMECs routinely generated two distinct cell populations. One population retained epithelial characteristics, while an emergent population spontaneously acquired a mesenchymal morphology and properties associated with cancer stem cells. [Neoplasia] Full Article

Pivotal Role for ROS Activation of p38 MAPK in the Control of Differentiation and Tumor-Initiating Capacity of Glioma-Initiating Cells
Scientists showed that reactive oxygen species (ROS)-mediated activation of p38 MAPK plays a pivotal role in the control of differentiation and tumor-initiating capacity of glioma-initiating cells derived from human glioblastomas. [Stem Cell Res] Abstract

Maintenance of the Stemness in CD44⁺ HCT-15 and HCT-116 Human Colon Cancer Cells Requires miR-203 Suppression
By manipulating the expression of CD44 in HCT-15 and HCT-116 cells, scientists found that the levels of several epithelial-mesenchymal transition activators and microRNA-203 (miR-203) were positively and negatively correlated with those of CD44, respectively. Further analyses revealed that miR-203 levels were repressed by Snail, which was shown to bind to specific E-box(es) present in the miR-203 promoter. In agreement, silencing miR-203 expression in wild-type HCT-116 human colon cancer cells also resulted in an increase of their stemness. [Stem Cell Res] Abstract

Stem Cells in the Skin and Their Role in Oncogenesis
Small populations of oncogenic stem cells termed as cancer stem cells or tumor-initiating cells have been identified in multiple tumors, including squamous cell carcinomas, and melanomas that can sustain tumor growth, underlie its malignant behavior and initiate distant metastases. These cells are controlled and regulated by the same pathways that are also responsible for maintenance and differentiation of normal stem cells. [J Eur Acad Dermatol Venereol] Abstract

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Kiadis Pharma Secures Manufacturing Services Agreement for Its Phase II Clinical Program with Blood Cancer Treatment ATIR™ with the German Red Cross Blood Donor Service
Kiadis Pharma B.V., a biopharmaceutical company developing treatments for blood cancers, announced that a Services Agreement has been signed with the German Red Cross Blood Donor Service Baden-Wuerttemberg-Hessen (GRCBDS) whereby GRCBDS will provide pharmaceutical development and GMP manufacturing services for Kiadis Pharma’s ongoing Phase II clinical study with ATIR™. [Kiadis Pharma B.V.] Press Release

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