Increased epithelial and serum expression of macrophage migration inhibitory factor (MIF) in gastric cancer: potential role of MIF in gastric carcinogenesis

Abstract

Aims: Macrophage migration inhibitory factor (MIF) is implicated in tumorigenesis. This study was conducted to determine whether MIF expression is associated with gastric pathology and whether MIF expression is increased in malignant gastric cells in vitro. Materials and methods: Patients with a normal gastric mucosa, Helicobacter pylori infected gastritis, intestinal metaplasia, and gastric adenocarcinoma were included. Immunohistochemistry and enzyme linked immunosorbent assay (ELISA) were used to determine MIF expression in gastric epithelial cells and MIF levels in serum, respectively. 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 supernatant and MIF mRNA in cultured cells were measured by ELISA and reverse transcriptionpolymerase chain reaction, respectively. Results: The percentage of MIF expressing epithelial cells was low in normal mucosa (12%) but substantially higher in gastritis (52%), intestinal metaplasia (66%), and gastric cancer (96%) (p,0.001, ANOVA). Serum MIF levels were low in patients with a normal mucosa (576 (82) pg/ml) but higher in patients with gastritis (2100 (349) pg/ml), intestinal metaplasia (4498 (253) pg/ml), and gastric cancer (9737 (1249) pg/ml) (p,0.001, ANOVA). There was a correlation between epithelial MIF expression and serum MIF levels (r = 0.776, p,0.001). In vitro, expression of MIF protein and mRNA was increased in malignant cells compared with non-malignant cells. Conclusions: Epithelial and serum MIF expression was progressively increased in H pylori induced gastritis, intestinal metaplasia, and gastric cancer, suggesting that MIF is involved in gastric carcinogenesis and may be a valuable biomarker for the early detection of gastric cancer.

Identification of macrophage migration inhibitory factor and human neutrophil peptides 1–3 as potential biomarkers for gastric cancer

“…Furthermore, our data suggest that serum MIF is elevated in the early stages of gastric cancer relative to relevant disease control subjects, a factor that is of considerable importance in establishing a useful diagnostic role for this potential biomarker. In agreement with the findings of He et al (2006), we find that tissue and serum levels of MIF are not strongly influenced by H. pylori.…”

“…In 2006 He et al (He et al, 2006) reported MIF overexpression in the tissue and serum of gastric cancer patients from Hong Kong. More recently Camlica et al (Camlica et al, 2008) reported elevated serum MIF in gastric cancer patients relative to healthy controls.…”

Macrophage Migration Inhibitory Factor Coordinates DNA Damage Response with the Proteasomal Control of the Cell Cycle

“…Moreover, MIF is frequently overexpressed in human tumors and was reported to possess tumor-promoting activity. [26][27][28][29][30][31][32][33][34][35][36][37] Importantly, these initial observations were confirmed by gene knockout studies that clearly demonstrated that MIF mediates many of its growth-and tumor-promoting effects via p53-dependent mechanisms. [38][39][40] Although a number of cell cycle-associated proteins such as Rb, E2Fs, p16, p21 and p27 were also found altered in MIF deficiency, the underlying mechanism of MIF activity remained elusive at first.…”

“…reported, 28,32,37,[47][48][49] and in some cases correlated with poor prognosis, 32,37,49 two reports indicated that aberrantly low levels of MIF in human tumors correlated with poor clinical outcome. 50,51 (2) Chemical one stage-and two stage-skin carcinogenesis experiments showed that MIF-deficiency leads to an increased rate of tumor formation in C57Bl/6 and 129Sv mice (Fingerle-Rowson G, unpublished).…”

Characteristics of B-lymphocytic infiltration in the peritumoral mucosa of the stomach in its cancer: Clinical and morphological aspects

“…Другие предполагают, что опухолеассоциированные лимфоциты и макрофаги могут быть связаны с опухолевой прогрессией [5][6][7][8]. При этом следует отметить, что большинство исследований связано с изучением роли Т-лимфоцитов и макрофагов в опухо-левой прогрессии [3,8,9], тогда как роль В-лимфоцитов остается практически неизученной. В связи с этим целью настоящего исследования явилось изучение особенностей перитуморальной инфильтрации слизистой оболочки же-лудка (СОЖ) В-лимфоцитами и их связь с клиническими характеристиками РЖ.…”