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Gastritis promotes an activated bone marrow-derived mesenchymal stem cell with a phenotype reminiscent of a cancer-promoting cell.

ABSTRACT: Bone marrow-derived mesenchymal stem cells (BM-MSCs) promote gastric cancer in response to gastritis. In culture, BM-MSCs are prone to mutation with continued passage but it is unknown whether a similar process occurs in vivo in response to gastritis.The purpose of this study was to identify the role of chronic gastritis in the transformation of BM-MSCs leading to an activated cancer-promoting phenotype.Age matched C57BL/6 (BL/6) and gastrin deficient (GKO) mice were used for isolation of stomach, serum and mesenchymal stem cells (MSCs) at 3 and 6 months of age. MSC activation was assessed by growth curve analysis, fluorescence-activated cell sorting and xenograft assays. To allow for the isolation of bone marrow-derived stromal cells and assay in response to chronic gastritis, IRG/Vav-1(Cre) mice that expressed both enhanced green fluorescent protein-expressing hematopoietic cells and red fluorescent protein-expressing stromal cells were generated. In a parabiosis experiment, IRG/Vav-1(Cre) mice were paired to either an uninfected Vav-1(Cre) littermate or a BL/6 mouse inoculated with Helicobacter pylori.GKO mice displayed severe atrophic gastritis accompanied by elevated gastric tissue and circulating transforming growth factor beta (TGF?) by 3 months of age. Compared to BM-MSCs isolated from uninflamed BL/6 mice, BM-MSCs isolated from GKO mice displayed an increased proliferative rate and elevated phosphorylated-Smad3 suggesting active TGF? signaling. In xenograft assays, mice injected with BM-MSCs from 6-month-old GKO animals displayed tumor growth. RFP+ stromal cells were rapidly recruited to the gastric mucosa of H. pylori parabionts and exhibited changes in gene expression.Gastritis promotes the in vivo activation of BM-MSCs to a phenotype reminiscent of a cancer-promoting cell.

SUBMITTER: Donnelly JM

PROVIDER: S-EPMC4301577 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Gastritis promotes an activated bone marrow-derived mesenchymal stem cell with a phenotype reminiscent of a cancer-promoting cell.

Donnelly Jessica M JM Engevik Amy C AC Engevik Melinda M Schumacher Michael A MA Xiao Chang C Yang Li L Worrell Roger T RT Zavros Yana Y

Digestive diseases and sciences 20131108 3

<h4>Background</h4>Bone marrow-derived mesenchymal stem cells (BM-MSCs) promote gastric cancer in response to gastritis. In culture, BM-MSCs are prone to mutation with continued passage but it is unknown whether a similar process occurs in vivo in response to gastritis.<h4>Aim</h4>The purpose of this study was to identify the role of chronic gastritis in the transformation of BM-MSCs leading to an activated cancer-promoting phenotype.<h4>Methods</h4>Age matched C57BL/6 (BL/6) and gastrin deficie ...[more]

PMID: 24202649

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Dataset Information

Gastritis promotes an activated bone marrow-derived mesenchymal stem cell with a phenotype reminiscent of a cancer-promoting cell.

Publications

Gastritis promotes an activated bone marrow-derived mesenchymal stem cell with a phenotype reminiscent of a cancer-promoting cell.

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