Abstract
Epithelial cancers are believed to originate from transformation of tissue stem cells. However, bone marrow-derived cells (BMDCs), which are frequently recruited to sites of tissue injury and inflammation, might also represent a potential source of malignancy. We show that although acute injury, acute inflammation, or transient parietal cell loss within the stomach do not lead to BMDC recruitment, chronic infection of C57BL/6 mice with Helicobacter, a known carcinogen, induces repopulation of the stomach with BMDCs. Subsequently, these cells progress through metaplasia and dysplasia to intraepithelial cancer. These findings suggest that epithelial cancers can originate from marrow-derived sources and thus have broad implications for the multistep model of cancer progression.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis
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Bone Marrow Cells / cytology*
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Bone Marrow Transplantation
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Carcinoma in Situ / pathology
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Cell Differentiation
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Cell Fusion
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Disease Progression
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Female
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Gastric Mucosa / chemistry
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Gastric Mucosa / pathology
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Gastritis / pathology*
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Helicobacter Infections / pathology*
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Helicobacter felis*
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Keratins / analysis
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Male
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Mesenchymal Stem Cells / physiology
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Metaplasia
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Mucins / analysis
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Muscle Proteins / analysis
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Parietal Cells, Gastric / physiology
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Peptides / analysis
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Phenotype
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Stem Cells / physiology*
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Stomach Neoplasms / pathology*
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Trefoil Factor-2
Substances
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Mucins
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Muscle Proteins
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Peptides
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TFF2 protein, mouse
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Trefoil Factor-2
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Keratins