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Digestive Diseases and Sciences
Erschienen in: Digestive Diseases and Sciences 3/2014

01.03.2014 | Original Article

Gastritis Promotes an Activated Bone Marrow-Derived Mesenchymal Stem Cell with a Phenotype Reminiscent of a Cancer-Promoting Cell

verfasst von: Jessica M. Donnelly, Amy C. Engevik, Melinda Engevik, Michael A. Schumacher, Chang Xiao, Li Yang, Roger T. Worrell, Yana Zavros

Erschienen in: Digestive Diseases and Sciences | Ausgabe 3/2014

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Abstract

Background

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.

Aim

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.

Methods

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-1Cre 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-1Cre mice were paired to either an uninfected Vav-1Cre littermate or a BL/6 mouse inoculated with Helicobacter pylori.

Results

GKO mice displayed severe atrophic gastritis accompanied by elevated gastric tissue and circulating transforming growth factor beta (TGFβ) 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 TGFβ 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.

Conclusions

Gastritis promotes the in vivo activation of BM-MSCs to a phenotype reminiscent of a cancer-promoting cell.
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Metadaten
Titel
Gastritis Promotes an Activated Bone Marrow-Derived Mesenchymal Stem Cell with a Phenotype Reminiscent of a Cancer-Promoting Cell
verfasst von
Jessica M. Donnelly
Amy C. Engevik
Melinda Engevik
Michael A. Schumacher
Chang Xiao
Li Yang
Roger T. Worrell
Yana Zavros
Publikationsdatum
01.03.2014
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 3/2014
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-013-2927-z

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