title: Spasmolytic polypeptide-expressing metaplasia (SPEM) in the gastric oxyntic mucosa does not arise from Lgr5-expressing cells.
abstract: OBJECTIVE
  Metaplastic lineages in the oxyntic mucosa of the stomach are critical preneoplastic precursors of gastric cancer. Recent studies have demonstrated that spasmolytic polypeptide-expressing metaplasia (SPEM) in the mouse oxyntic mucosa arises from transdifferentiation of mature gastric chief cells. Other investigations of intestinal progenitor cells have shown that cells demonstrating transcriptional activity for leucine-rich repeat containing G-protein-coupled receptor 5 (Lgr5) in the intestine, colon and gastric antrum function as adult stem cells. We have now investigated whether cells demonstrating Lgr5 transcriptional activity in the oxyntic mucosa of mice might be responsible for development of metaplasia.
  
  
  METHODS
  Lgr5-EGFP-IRES-Cre(ERT2/+);Rosa26R mice were used to examine the distribution of Lgr5 transcriptionally active cells in the normal oxyntic mucosa as well as after treatment with DMP-777 or L-635 to induce acute SPEM. Lineage mapping was performed to determine if Lgr5-expressing cells gave rise to SPEM.
  
  
  RESULTS
  Cells expressing transcriptional activity for Lgr5 in the oxyntic mucosa were present as scattered rare cells only along the lesser curvature of the stomach. These cells also stained for markers of chief cells (intrinsic factor and pepsinogen) but never showed any staining for proliferative markers (Ki-67). In Lgr5-EGFP-IRES-Cre(ERT2/+);Rosa26R mice induced with tamoxifen, treatment with either DMP-777 or L-635 to induce acute oxyntic atrophy caused induction of SPEM, but no lineage mapping into SPEM from Lgr5-expressing cells was observed.
  
  
  CONCLUSIONS
  The results indicate that, while chief cells with Lgr5 transcriptional activity are present along the lesser curvature of the gastric oxyntic mucosa, they are not responsible for production of metaplasia.
authors.affiliation: Nashville VA Medical Center and the Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2733, USA.
authors.forename: Ki Taek
authors.initials: KT
authors.lastname: Nam
authors.forename: Ryan L
authors.initials: RL
authors.lastname: O'Neal
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Coffey
authors.forename: Paul E
authors.initials: PE
authors.lastname: Finke
authors.forename: Nick
authors.initials: N
authors.lastname: Barker
authors.forename: James R
authors.initials: JR
authors.lastname: Goldenring
mesh_terms: D000818:Animals; D001384:Azetidines; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019070:Cell Lineage; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008679:Metaplasia; D051379:Mice; D010295:Parietal Cells, Gastric / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000378:metabolism*; D010879:Piperazines; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001384:Azetidines; D015415:Biomarkers; D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; C493597:Lgr5 protein, mouse; D010455:Peptides; D010879:Piperazines; D043562:Receptors, G-Protein-Coupled; C451060:spasmolytic polypeptide; C105999:DMP 777; D001616:beta-Galactosidase