University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Division of Gastroenterology, Department of Medicine; Department of Cancer Biology
Publication Date
2013-9
Document Type
Article
Subjects
Animals; Cell Differentiation; Epithelial Cells; Ethanol; Gastritis; Helicobacter Infections; Helicobacter felis; Male; Mesenchymal Stromal Cells; Mice; Mice, Inbred C57BL; Receptors, CXCR4; Signal Transduction; Stomach; Stomach Neoplasms
Disciplines
Cancer Biology | Cell Biology | Digestive System Diseases | Gastroenterology | Neoplasms | Oncology
Abstract
BACKGROUND: Helicobacter infection is the main risk factor in developing gastric cancer. Mesenchymal stem cells (MSCs) are non-hematopoietic stromal cells, which are able to differentiate into different cell lineages. MSC contribute to cancer development by forming the tumor directly, contributing to the microenvironment, or by promoting angiogenesis and metastasis. CXCR4/SDF-1 axis is used by MSC in trafficking, homing, and engraftment at chronic inflammation sites, and plays an important role in tumorigenesis.
AIM: To determine if CXCR4 receptor has a role in MSC contribution to the development of Helicobacter-mediated gastric cancer.
METHODS: SDF-1 and CXCR4 expression in mouse gastric mucosa in the setting of acute and chronic inflammation was measured using RT-PCR. Mouse culture-adapted MSC express CXCR4. Wild-type C57BL/6 mice infected with Helicobacter felis for 6 months or controls were given IV injections of CXCR4 knock-down MSC. Animals were followed for another 4 months. Homing of MSC in the stomach was quantified using RT-PCR. MSC differentiation into gastric epithelia lineages was analyzed using immunohistochemistry and fluorescent in situ hybridization.
RESULTS: CXCR4 and SDF-1 are both upregulated in the settings of Helicobacter-induced chronic gastric inflammation. CXCR4 is fully required for homing of MSC to the stomach in acute gastric inflammation, but only partially in Helicobacter-induced gastric cancer. MSC lead to gastric intraepithelial neoplasia as early as 10 months of Helicobacter infection.
CONCLUSIONS: Our results show that MSC have a tumorigenic effect by promoting an accelerated form of gastric cancer in mice. The engraftment of MSC in chronic inflammation is only partially CXCR4-dependent.
Keywords
Gastric cancer, Helicobacter, Mesenchymal stem cells, CXCR4, SDF-1
DOI of Published Version
10.1007/s10620-013-2782-y
Source
Dig Dis Sci. 2013 Sep;58(9):2466-77. doi: 10.1007/s10620-013-2782-y. Link to article on publisher's site
Related Resources
Journal/Book/Conference Title
Digestive diseases and sciences
PubMed ID
23873382
Repository Citation
Stoicov, Calin; Li, Hanchen; Liu, Jian Hua; and Houghton, JeanMarie, "Mesenchymal stem cells utilize CXCR4-SDF-1 signaling for acute, but not chronic, trafficking to gastric mucosal inflammation" (2013). University of Massachusetts Medical School Faculty Publications. 465.
https://escholarship.umassmed.edu/faculty_pubs/465
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License
Included in
Cancer Biology Commons, Cell Biology Commons, Digestive System Diseases Commons, Gastroenterology Commons, Neoplasms Commons, Oncology Commons