title: The homing receptor CD44 is involved in the progression of precancerous gastric lesions in patients infected with Helicobacter pylori and in development of mucous metaplasia in mice.
abstract: Infection with Helicobacter pylori (H. pylori) leads to inflammatory events that can promote gastric cancer development. Immune cells transition from the circulation into the infected mucosa through the interaction of their receptors and ligands in the endothelial compartment. CD44 expression is increased in advanced gastric lesions. However, the association of this molecule with the progression of these lesions over time has not been investigated. In addition, there is a lack of understanding of the CD44-dependent cellular processes that lead to gastritis, and possibly to gastric cancer. Here we studied H. pylori-positive subjects with gastric lesions that ranged from multifocal atrophic gastritis to dysplasia to determine gene expression changes associated with disease progression over a period of 6 years. We report that CD44 expression is significantly increased in individuals whose gastric lesions progressed along the gastric precancerous cascade. We also show that CD44-/- mice develop less severe and less extensive H. pylori-induced metaplasia, and show fewer infiltrating Gr1+ cells compared to wild type mice. We present data suggesting that CD44 is associated with disease progression. Mechanisms associated with these effects include induction of interferon gamma responses.
authors.affiliation: Stanley S. Scott Cancer Center, LSUHSC, New Orleans, LA, USA.
authors.forename: Jone
authors.initials: J
authors.lastname: Garay
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: M Blanca
authors.initials: MB
authors.lastname: Piazuelo
authors.affiliation: Stanley S. Scott Cancer Center, LSUHSC, New Orleans, LA, USA.
authors.forename: Sumana
authors.initials: S
authors.lastname: Majumdar
authors.affiliation: Stanley S. Scott Cancer Center, LSUHSC, New Orleans, LA, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Stanley S. Scott Cancer Center, LSUHSC, New Orleans, LA, USA.
authors.forename: Jimena
authors.initials: J
authors.lastname: Trillo-Tinoco
authors.affiliation: Stanley S. Scott Cancer Center, LSUHSC, New Orleans, LA, USA; Department of Pathology, LSUHSC, New Orleans, LA, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Del Valle
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Schneider
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Alberto G
authors.initials: AG
authors.lastname: Delgado
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Keith T
authors.initials: KT
authors.lastname: Wilson
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Pelayo
authors.initials: P
authors.lastname: Correa
authors.affiliation: Stanley S. Scott Cancer Center, LSUHSC, New Orleans, LA, USA; Department of Pediatrics, LSUHSC New Orleans, LA, USA. Electronic address: jzabal@lsuhsc.edu.
authors.forename: Jovanny
authors.initials: J
authors.lastname: Zabaleta
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D005757:Gastritis, Atrophic / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D016481:Helicobacter Infections / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011230:Precancerous Conditions / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D013997:Time Factors
chemical_list: D000950:Antigens, Ly; C497483:CD44 protein, human; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; C480309:Ly6G antigen, mouse; D007371:Interferon-gamma
keywords: CD44; Gastric cancer; Gastritis; Inflammation