Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/86614
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Stoma cell-derived factor-1 overexpression induces gastric dysplasia through expansion of stromal myofibroblasts and epithelial progenitors |
Author: | Shibata, W. Ariyama, H. Westphalen, C. Worthley, D. Muthupalani, S. Asfaha, S. Dubeykovskaya, Z. Quante, M. Fox, J. Wang, T. |
Citation: | Gut, 2013; 62(2):192-200 |
Publisher: | BMJ Publishing Group |
Issue Date: | 2013 |
ISSN: | 0017-5749 1468-3288 |
Statement of Responsibility: | Wataru Shibata, Hiroshi Ariyama, Christoph Benedikt Westphalen, Daniel L Worthley, Sureshkumar Muthupalani, Samuel Asfaha, Zinaida Dubeykovskaya, Michael Quante, James G Fox, Timothy C Wang |
Abstract: | Objective: Stromal cell-derived factor-1 (SDF-1/CXCL12), the main ligand for CXCR4, is overexpressed in human cancer. This study addressed the precise contribution of SDF-1 to gastric carcinogenesis. Design: SDF-1 transgenic mice were created and a Helicobacter-induced gastric cancer model was used in combination with H/K-ATPase-IL-1β mice. Gastric tissue was analysed by histopathology and cells isolated from the stomach were analysed by molecular biological methods. Results: Analysis of the H/K-ATPase/SDF-1 transgenic (SDF-Tg) mice showed that SDF-1 overexpression results in significant gastric epithelial hyperproliferation, mucous neck cell hyperplasia and spontaneous gastric dysplasia (wild-type mice 0/15 (0%) vs SDF-Tg mice 4/14 (28.6%), p=0.042, Fisher exact test) but has minimal effects on inflammation. SDF-Tg mice also showed a dramatic expansion of α-smooth muscle actin-positive myofibroblasts and CXCR4-expressing gastric epithelial cells in the progenitor zone, both of which preceded the development of significant gastritis or dysplasia. Gremlin 1-expressing mesenchymal stem cells, the putative precursors of myofibroblasts, were also increased within the dysplastic stomachs of SDF-Tg mice and showed chemotaxis in response to SDF-1 stimulation. SDF-1 overexpression alone resulted in minimal recruitment of haematopoietic cells to the gastric mucosa, although macrophages were increased late in the disease. When SDF-Tg mice were crossed with H/K-ATPase-IL-1β mice or infected with Helicobacter felis, however, there were dramatic synergistic effects on recruitment of bone marrow-derived cells and progression to preneoplasia. Conclusion: Activation of the SDF-1/CXCR4 axis can contribute to early stages of carcinogenesis primarily through recruitment of stromal cells and modulation of the progenitor niche. |
Keywords: | Gastric Mucosa Mesenchymal Stem Cells Animals Mice, Inbred C57BL Mice, Transgenic Mice Stomach Neoplasms Precancerous Conditions Disease Models, Animal Intercellular Signaling Peptides and Proteins Receptors, CXCR4 RNA, Messenger Enzyme-Linked Immunosorbent Assay Immunohistochemistry Gene Expression Regulation Chemokine CXCL12 Myofibroblasts Real-Time Polymerase Chain Reaction |
Rights: | © 2013, BMJ Publishing Group Ltd and the British Society of Gastroenterology |
DOI: | 10.1136/gutjnl-2011-301824 |
Published version: | http://dx.doi.org/10.1136/gutjnl-2011-301824 |
Appears in Collections: | Aurora harvest 2 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.