Increased Expression of Macrophage Migration Inhibitory Factor (MIF)in Epithelium and Serum in Gastric Cancer:Potential Role of MIF in Gastric Carcinogenesis

摘要

AIM Macrophage migration inhibitory factor (MIF),known to play a pivotal role in inflammatory and immune diseases,is now implicated in tumorogenesis.This study aimed to determine if MIF expression is associated with the progression of gastric pathology and to determine if there is a difference in MIF expression between non-malignant and malignant gastric cells in vitro.METHODS Ninety patients(M/F,54/36,age,56±16 years),15 with normal gastric mucosa,15 with H.pylori-associated chronic antral gastritis,20 with intestinal metaplasia in antra,and 40 with antral adenocarcinoma,were enrolled in this study.Immunohistochemistry was used to determine MIF expression in epithelial cells of gastric antra,and enzyme-linked immunosorbent assay (ELISA) was used to measure MIF concentration in serum.Five gastric cancer cell lines (AGS,MKN-45,MKN-28,MGC-803 and SGC-7901) and one non-malignant gastric cell line (GES-1) were cultured for 24 hours.MIF protein in the super natant was measured by ELISA,and MIF mRNA in cultured cells was determined by reverse transcription-polymerase chain reaction.RESULTS MIF expression in epithelial cells was weak in normal mucosa (12%),but increasingly elevated in gastritis (52%),intestinal metaplasia (66%) and gastric cancer(96%)(P<0.001,ANOVA).Serum MIF level was also increased with the pathological changes(576±82 pg/ml in normal mucosa,2 100±349 pg/ml in gastritis,4 498±253 pg/ml in intestinal metaplasia and 9 737±1 249 pg/ml in gastric cancer,P<0.001,ANOVA).There was a significant correlation between epithelial MIF expression and serum MIF level(R=0.776,P＜0.001).In vitro,expression of MIF protein and mRNA was increased in malignant cells,compared to non-malignant cells.CONCLUSIONS Epithelial and serum MIF expression is significantly increased in H.pylori-associated gastritis,and particularly in intestinal metaplasia and gastric cancer,implying that MIF is involved in the gastric carcinogenesis.