The effect of nitric oxide, growth factors, and estrogen on gastric cell migration.
BACKGROUND
To study gastric epithelial cell migration during nitric oxide (NO) and growth factor treatment, simulating inflammation and infection. Also, the effects of estrogen on migration of different malignant and nonmalignant gastric epithelial cell lines were explored.


METHODS
Isolated primary cultured rabbit gastric epithelial cells, rat gastric mucosal cells, human gastric adenocarcinoma cells, and human colon adenocarcinoma cells (WiDr) were cultured to confluency in appropriate media (5% CO2, 37 degrees C). The cells were treated by hepatocyte growth factor (HGF), transforming growth factor-alpha (TGF-alpha) and keratinocyte growth factor (KGF), with and without sodium nitroprusside (SNP, NO donor) or 17beta-estradiol. Caspase-3 activity and cell viability and migration speed after wounding were measured.


RESULTS
HGF was the most potent growth factor to stimulate migration. SNP dose-dependently decreased the speed of migration. HGF and TGF-alpha were able to overcome the SNP-induced inhibition of migration, whereas KGF was not. SNP also induced caspase-3 activity, which was inhibited by HGF and TGF-alpha. 17beta-estradiol decreased migration in all epithelial cells, but the decrease was more profound in malignant cell lines. HGF could overcome the estrogen retarded migration.


CONCLUSIONS
Growth factors can overcome NO-induced retardation of cell migration and inhibit NO-induced caspase-3 activity, which altogether might also have physiological significance in in vivo inflammation and in gastric cancer. The more profound decrease in migration speed of gastric adenocarcinoma cell line may suggest that estrogen might be one of the protective factor against female gastric adenocarcinoma before menopausal age.
Nylander-Koski
Outi
O
Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland.
Kiviluoto
Tuula
T
Puolakkainen
Pauli
P
Kivilaakso
Eero
E
Mustonen
Harri
H
D000230:Adenocarcinoma; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D013274:Stomach Neoplasms; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D036341:Intercellular Signaling Peptides and Proteins; D020030:Nitric Oxide Donors; D011960:Receptors, Estrogen; D016211:Transforming Growth Factor alpha; D051523:Fibroblast Growth Factor 7; D009599:Nitroprusside; D009569:Nitric Oxide; D004958:Estradiol; D017228:Hepatocyte Growth Factor; D053148:Caspase 3