H. pylori infection-induced MSC differentiation into CAFs promotes epithelial-mesenchymal transition in gastric epithelial cells

• Published in: International journal of molecular medicine Vol. 32; no. 6; pp. 1465 - 1473
• Main Authors: ZHANG, QIANG, WANG, MEI, HUANG, FENG, YANG, TINGTING, CAI, JIE, ZHANG, XU, ZHU, WEI, QIAN, HUI, XU, WENRONG
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.12.2013; Spandidos Publications UK Ltd
• Subjects: Angiogenesis; Apoptosis - drug effects; cancer- associated fibroblast; Cell culture; Cell Differentiation - drug effects; Cell Line; Cell Proliferation - drug effects; Cell Shape - drug effects; Colony-Forming Units Assay; Culture Media, Conditioned - pharmacology; Cytokines - metabolism; Epithelial Cells - microbiology; Epithelial Cells - pathology; epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - drug effects; Experiments; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - microbiology; Fibroblasts - pathology; Gastric cancer; Gene expression; Helicobacter Infections - microbiology; Helicobacter Infections - pathology; Helicobacter pylori; Helicobacter pylori - physiology; human umbilical cord-mesenchymal stem cells; Humans; Infections; Inflammation; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Metastasis; Morphology; Penicillin; Stem cells; Stomach - pathology; Stomach Neoplasms - microbiology; Studies; Tumor Suppressor Proteins - metabolism
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2013.1532

Mesenchymal stem cell (MSC) tropism to injured tissue sites in response to inflammation and wounds has been suggested. MSC activation and recruitment by Helicobacter pylori (H. pylori)-infected gastrointestinal epithelial cells has been demonstrated. As a component of the chronic gastritis microenvironment, MSCs play critical roles in the development of H. pylori-associated gastric mucosal lesions/malignancies. However, the mechanisms responsible for this process remain largely unknown. In this study, we demonstrate that H. pylori infection induces the differentiation of MSCs into cancer-associated fibroblast (CAF)-like cells. H. pylori-infected MSCs possessed an altered cytokine profile and induced epithelial-mesenchymal transition in gastric epithelial cells, leading to destroyed cell junctions, enhanced cell migration, reduced cell apoptosis and increased oncogenic potential. In conclusion, our findings indicate that H. pylori infection may cause gastric lesions/malignancies by inducing the differentiation of MSCs into CAFs and suggest a novel mechanism of action and role of MSCs in the development and progression of gastric cancer.