University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Division of Gastroenterology, Department of Medicine; Department of Cancer Biology

Date

9-2013

Document Type

Article

Medical Subject Headings

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.

Rights and Permissions

Citation: 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

Link to Article in PubMed

Keywords

Gastric cancer, Helicobacter, Mesenchymal stem cells, CXCR4, SDF-1

Creative Commons License

Creative Commons Attribution-Noncommercial 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License

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