Abstract: Objective The aim of this study was to investigate the expression of heparanase(HPA), monocyte chemokine-1(MCP-1)and chemokine receptor 2(CCR2)in human gastric cancer, and to explore the molecular mechanism of HPA induced invasion and metastasis of human gastric cancer cells. Methods Immunohistochemical method was used to detect the expression of HPA, MCP-1 and CCR2 proteins in 74 cases of human gastric cancer tissues. Human gastric cancer MGC803 cells, MGC803-HPA cells(HPA protein overexpressing cell line), SGC7901 cells, and SGC7901-HPA(-)cells(HPA protein knockdown cell line)were cultured. MGC803 cells and SGC7901 cells were used as the experimental group, MGC803-HPA cells and SGC7901-HPA(-)cells were used as the control group. MTT experiment was used to detect the optimal inhibitory concentration of CCR2 inhibitor(RS504393)in MGC803-HPA cells. Western blot experiment was used to detect the expression of various proteins in human gastric cancer cells. The scratch experiment and Transwell invasion assay were used to detect the abilities of migration and invasion in human gastric cancer cells. Results The positive expression of HPA and MCP-1/CCR2 proteins in human gastric cancer tissues was closely related to the location, degree of differentiation, depth of invasion and lymph node metastasis of human gastric cancer(P＜0.05). There is a positive correlation between HPA protein expression and MCP-1/CCR2 protein expression in human gastric cancer tissues(P＜0.05). HPA overexpression could promote cell migration and invasion(P＜0.05), and the CCR2 inhibitor RS504393 could inhibit the migration and matrix invasion ability enhanced by HPA overexpression in gastric cancer cells(P＜0.05). Conclusion HPA protein is an upstream factor that induces the expression of MCP-1/CCR2 protein in human gastric cancer. HPA induces invasion and metastasis of human gastric cancer by up-regulating MCP-1/CCR2 protein expression.

Key words: Gastric cancer, Heparanase, Monocyte chemokine-1, Chemokine receptor 2, Invasion, Metastasis