Celecoxib inhibits CD133-positive cell migration via reduction of CCR2 in Helicobacter pylori-infected Mongolian gerbils.
OBJECTIVE
To see whether celecoxib prevents gastric cancer occurrence by disrupting the progression of chronic gastritis into gastric carcinoma through its inhibition of the migration of CD133-positive cells, one of the surface markers of bone marrow-derived cells, in Helicobacter pylori-infected gerbils.


METHODS
70 gerbils were divided into six groups. Group 1 gerbils served as control (n = 6). 10 gerbils were given N-methyl-N-nitrosourea (MNU), 30 ppm (group 2). 6 short-term Helicobacter pylori-infected gerbils (group 3) were sacrificed after 8 weeks of H. pylori infection and 6 long-term H. pylori-infected gerbils were sacrificed after 42 weeks of H. pylori infection (group 4). 20 gerbils were given MNU pretreatment and long-term H. pylori infection (group 5). In addition, after H. pylori inoculation, 22 gerbils also received a celecoxib in their diet (group 6). CD133 and CCR2 expression in gastric tissues was evaluated by Western blot analysis and immunostaining.


RESULTS
CD133-positive cells were mainly localized in the bottom of the gastric epithelial cells. CD133-positive cells also migrated into gastric cancer tissues in this model. CD133-positive cells in MNU-pretreated H. pylori-infected gerbils were significantly increased compared to those in H. pylori short-term infected gerbils. Celecoxib treatment significantly reduced CD133-positive cell migration and CCR2 expression levels. CD133- and CCR2-positive cells were colocalized in H. pylori-infected gastritis and gastric cancer tissues. Celecoxib treatment significantly reduced the number of CD133- and CCR2-positive cells.


CONCLUSIONS
Celecoxib inhibits CD133-positive cell migration via the reduction of CCR2 in this model. Further studies are needed to clarify the precise mechanisms driving H. pylori infection-induced CD133-positive cell migration and its link to the progression of chronic gastritis into gastric cancer.
Futagami
Seiji
S
Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School, Tokyo, Japan. seiji.futagami@gmail.com
Hamamoto
Tatsuhiko
T
Shimpuku
Mayumi
M
Nagoya
Hiroyuki
H
Kawagoe
Tetsuro
T
Horie
Akane
A
Shindo
Tomotaka
T
Gudis
Katya
K
Sakamoto
Choitsu
C
D000071916:AC133 Antigen; D000230:Adenocarcinoma / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015153:Blotting, Western; D000068579:Celecoxib; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects*; D018450:Disease Progression; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005756:Gastritis / Q000150:complications / Q000503:physiopathology; D005849:Gerbillinae; D006023:Glycoproteins / Q000378:metabolism*; D016481:Helicobacter Infections / Q000473:pathology / Q000503:physiopathology*; D016480:Helicobacter pylori; D007150:Immunohistochemistry; D015994:Incidence; D010455:Peptides / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors*; D013274:Stomach Neoplasms / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013449:Sulfonamides / Q000494:pharmacology*; D014018:Tissue Distribution
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D010455:Peptides; D011720:Pyrazoles; D054390:Receptors, CCR2; D013449:Sulfonamides; D000068579:Celecoxib