Abstract
OBJECTIVES: To explore the role of tumour-associated macrophages (TAMs) in cardia carcinoma progression and the related mechanisms. METHODS: Cancer tissue and pericancer tissue samples from 80 patients with cardia carcinoma who underwent D2 radical surgery between January 2014 and January 2015 at Putian First Hospital were selected. Tissue microarrays were fabricated, and immunohistochemistry technology was used to detect the infiltration of TAMs (CD163 as a marker) and to analyse their relationship with the clinicopathological characteristics of the patients. The THP-1 monocyte cell line was used to induce differentiation into M2-type TAMs, co-cultured with gastric cancer cell lines AGS and MKN-45, and the effect of TAMs on the invasive ability of gastric cancer cells was detected by Transwell assay. Western blotting was used to detect the expression of matrix metalloproteinase-2 (MMP-2) and its inhibitor tissue inhibitor of metalloproteinase-3 (TIMP-3) in the microarrayed tissues. RESULTS: The immunohistochemical results showed that the infiltration density of CD163-positive TAMs in cardia carcinoma tissues was significantly higher than that in pericancerous tissues (P < 0.01). The high infiltration of TAMs closely correlated with the tumour length and diameter ≥ 5 cm, deep tumour infiltration, lymph node metastasis, and late TNM staging (all P < 0.05). Co-culture experiments showed that gastric cancer cells co-cultured with M2-type TAMs exhibited a stronger invasive ability, and the number of invasive cells was significantly higher than that in the control group (P < 0.001). Western blot analysis revealed that MMP-2 protein expression was significantly upregulated in gastric cancer cells in the co-culture group, whereas TIMP-3 protein expression was downregulated. CONCLUSIONS: TAMs highly infiltrate into cardia carcinoma tissues and are associated with poor prognosis. TAMs promote the invasive and metastatic ability of gastric cancer cells by regulating epithelial-mesenchymal transition and modulating MMP-2/TIMP-3 expression.