Helicobacter pylori infection targets adherens junction regulatory proteins and results in increased rates of migration in human gastric epithelial cells.
The human gastric pathogen Helicobacter pylori attaches to antral epithelial cells in vivo. Cultured human antral epithelial cells, AGS and NCI-N87 cell lines, were grown in the absence or presence of H. pylori and compared with respect to gene transcript levels, protein expression, organization of the actin cytoskeleton, and the regulation of cell migration. The Clontech Neurobiology array detected differentially expressed transcripts, while Western blots were used to investigate related changes in protein levels. Infection with H. pylori consistently upregulated annexin II, S100 A7, Rho-GTP, and IQGAP-1, whereas SSTR-1 was downregulated upon H. pylori infection. In the adherens junction, E-cadherin and IQGAP-1 were translocated from the plasma membrane to intracellular vesicles. The primary and NCI-N87 cells were similar with respect to cell-cell and cell-matrix adhesion and cell migratory behavior; in contrast the AGS cells were significantly different from the primary gastric epithelial cell preparations, and thus caution must be used when using this cell line for studies of gastric disease. These studies demonstrate a correlation between H. pylori infection and alterations to epithelial cell adhesion molecules, including increased levels of Rho-GTP and cell migration. These data indicate that destabilizing epithelial cell adherence is one of the factors increasing the risk of H. pylori-infected individuals developing gastric cancer.
Department of Physiology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, B.C. V6T 1Z3, Canada.
Victoria S
VS
Conlin
Susan B
SB
Curtis
Ying
Y
Zhao
Edwin D W
ED
Moore
Valerie C
VC
Smith
R Mark
RM
Meloche
B Brett
BB
Finlay
Alison M J
AM
Buchan
D022005:Adherens Junctions / Q000378:metabolism*; D000328:Adult; D001422:Bacterial Adhesion; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000382:microbiology* / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011706:Pyloric Antrum / Q000166:cytology / Q000382:microbiology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D014774:Virulence
D011506:Proteins; D043562:Receptors, G-Protein-Coupled