Intestinal Cell News Volume 1.00 | Mar 13 2015

Vascular Endothelial Growth Factor C Disrupts the Endothelial Lymphatic Barrier to Promote Colorectal Cancer Invasion
Scientists investigated vascular endothelial growth factor C signaling and lymphatic barriers in human tumor tissues and mice with orthotopic colorectal tumors. [Gastroenterology] Abstract

Epithelial-Derived IL-18 Regulates Th17 Cell Differentiation and Foxp3⁺ Treg Cell Function in the Intestine
Researchers demonstrated that interleukin-18 (IL-18)R1 expression is enhanced on both effector and regulatory CD4⁺ T cells in the intestinal lamina propria, with T helper type 17 (Th17) cells exhibiting particularly high levels. During steady state, intestinal epithelial cells constitutively secreted IL-18 that acts directly on IL-18R1-expressing CD4⁺ T cells to limit colonic Th17 cell differentiation, in part by antagonizing IL-1R1 signaling. [Mucosal Immunol] Abstract

Characterization of LGR5 Stem Cells in Colorectal Adenomas and Carcinomas
Researchers used in situ hybridization to specifically examine LGR5 mRNA expression in a panel of human adenoma and carcinoma samples. They found that a small number of cells express LGR5 at the base of normal colonic crypts. [Sci Rep] Full Article

The Role of MicroRNA-1274a in the Tumorigenesis of Gastric Cancer: Accelerating Cancer Cell Proliferation and Migration via Directly Targeting FOXO4
Scientists examined the effect of microRNA (miR)-1274a on gastric cancer cells. They found that miR-1274a was overexpressed in gastric cancer tissues or gastric cancer cells including HGC27, MGC803, AGS, and SGC-7901 by qRT-PCR analysis. Transfection of miR-1274a markedly promoted gastric cancer cells proliferation and migration as well as induced epithelial-mesenchymal transition of cancer cells targeting FOXO4. [Biochem Bioph Res Co] Abstract

Different Apoptotic Pathways Activated by Oxaliplatin in Primary Astrocytes vs. Colo-Rectal Cancer Cells
In vitro, the authors examined cell-specific activation apoptotic pathways in normal nervous cells (astrocytes) vs. colon-cancer cells (HT-29). They compared the apoptotic signals evoked by oxaliplatin in astrocytes and HT-29 analyzing the intrinsic and extrinsic apoptotic pathways. [Int J Mol Sci]
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Tumor Protein D52-Like 2 Accelerates Gastric Cancer Cell Proliferation In Vitro
Tumor protein D52-like 2 (TPD52L2) was found to be widely expressed in several gastric cancer cell lines. An efficient knockdown of TPD52L2 by a specific short hairpin RNA loaded in lentivirus resulted in a remarkable reduction in cell proliferation in both MGC80-3 and SGC-7901 cell lines with high TPD52L2 expression, but a slight or little reduction in the proliferation of MKN-28 and AGS cells with low TPD52L2 expression. [Cancer Biother Radio] Abstract

Intestinal Stem Cell and Organoid Research

Injury-Stimulated Hedgehog Signaling Promotes Regenerative Proliferation of Drosophila Intestinal Stem Cells
Researchers showed that injury induced Hedgehog (Hh) signaling in enteroblasts promotes intestinal stem cell proliferation in Drosophila melanogaster adult midgut. Elevated Hh signaling by patched mutations drove intestinal stem cell proliferation noncell autonomously. [J Cell Biol] Abstract | Editorial

Distinct Human Stem Cell Populations in Small and Large Intestine
The authors examined intrinsic differences between primary epithelial cells isolated from human fetal small and large intestine, after in vitro expansion, using the Wnt agonist R-spondin 2. They utilized flow cytometry, fluorescence-activated cell sorting, gene expression analysis and a three-dimensional in vitro differentiation assay to characterize their stem cell properties. [PLoS One] Full Article

A Human Colonic Crypt Culture System to Study Regulation of Stem Cell-Driven Tissue Renewal and Physiological Function
Researchers describe methods to establish 3D cultures of intact human colonic crypts and conduct real-time imaging of intestinal tissue renewal, cellular signaling, and physiological function, in conjunction with manipulation of gene expression by lentiviral or adenoviral transduction. Visualization of mRNA- and protein-expression patterns in cultured human colonic crypts, and cross-validation with crypts derived from fixed mucosal biopsies, is also described. [Methods Mol Biol] Abstract

Intestinal Dendritic Cells
The authors discuss the recent findings relating to intestinal dendritic cells, in particular the importance of dendritic cells in sensing the intestinal microenvironment and the consequences for health and disease. [Curr Opin Gastroen] Abstract

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MSD: New NICE Guidance on Biologics Expands Treatment Options for Patients with Moderately to Severely Active Ulcerative Colitis
The National Institute for Health and Care Excellence (NICE) has issued final guidance recommending the use of biologic therapies for the treatment of moderately to severely active ulcerative colitis in adult patients. [National Institute for Health and Care Excellence (Business Wire)] Press Release

Exact Sciences and Ironwood Pharmaceuticals Enter Co-Promotion Agreement for Cologuard^®
Exact Sciences Corp. and Ironwood Pharmaceuticals, Inc. announced an agreement to co-promote Exact Sciences’ Cologuard^®, the first and only FDA-approved noninvasive stool DNA screening test for colorectal cancer. [Ironwood Pharmaceuticals, Inc.] Press Release

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NEW Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

NEW Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

NEW Postdoctoral Positions – Innate Immunity and Intestinal Inflammation (Yale University School of Medicine)

NEW Postdoctoral Fellow – Intestinal Epithelial Cell-Innate Immune Crosstalk (University of Colorado Anschutz Medical Campus)

NEW Assistant Professor – Regenerative Medicine (University of Nebraska Medical Center)

NEW Postdoctoral Fellow – Adult Stem Cells of the Gastro-Intestinal Tract (University Hospital Carl Gustav Carus Dresden)

NEW Postdoctoral Positions – Microbiota in Cancer (Mount Sinai School of Medicine)

NEW Assistant/Associate Professors – Gastroenterology (North Carolina State University College of Veterinary Medicine)

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