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

Cancer Lett. 2016 Feb 1;371(1):90-8. doi: 10.1016/j.canlet.2015.10.037. Epub 2015 Nov 27.

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.

Keywords: CD44; Gastric cancer; Gastritis; Inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / metabolism
  • Cells, Cultured
  • Chemotaxis, Leukocyte
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Gastric Mucosa / immunology
  • Gastric Mucosa / metabolism*
  • Gastric Mucosa / microbiology
  • Gastric Mucosa / pathology
  • Gastritis, Atrophic / diagnosis
  • Gastritis, Atrophic / genetics
  • Gastritis, Atrophic / immunology
  • Gastritis, Atrophic / metabolism*
  • Gastritis, Atrophic / microbiology
  • Helicobacter Infections / diagnosis
  • Helicobacter Infections / genetics
  • Helicobacter Infections / immunology
  • Helicobacter Infections / metabolism*
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / immunology
  • Helicobacter pylori / pathogenicity*
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / immunology
  • Hyaluronan Receptors / metabolism*
  • Interferon-gamma / metabolism
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Mice, Knockout
  • Neutrophil Infiltration
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Precancerous Conditions / diagnosis
  • Precancerous Conditions / genetics
  • Precancerous Conditions / immunology
  • Precancerous Conditions / metabolism*
  • Precancerous Conditions / microbiology
  • Signal Transduction
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / microbiology
  • Time Factors

Substances

  • Antigens, Ly
  • CD44 protein, human
  • Cd44 protein, mouse
  • Hyaluronan Receptors
  • Ly6G antigen, mouse
  • Interferon-gamma