Expression Of IL-8and Its Receptors CXCR1/CXCR2in Angiogenesis Of Gastric Cancer

Objective:To study the expression of CXCL8and its receptors CXCR1, CXCR2in gastritis/gastric cancer in peripheral blood and gastric biopsy of patients,detect the levels of CXCL8, CXCR1, CXCR2mRNA in peripheral blood and gastric biopsy,analyze mutual relations with CXCL8, CXCR1, CXCR2mRNA Hp CagA and VacA and angiogenesis,explore molecular mechanisms of CXCL8, CXCR1, CXCR2after HP infection induced chronic gastritis, gastric cancer.Methods:Typical patients in HP infection with18cases of chronic gastritis,17cases of gastric ulcer patients,44cases of patients with gastric cancer,(24cases of intestinal type gastric,20cases of cancer diffuse gastric cancer) and12cases of normal blood donors control were selected,and the concentration of CXCL8in serum was detected by ELISA;the level of CXCL8, CXCR1, CXCR2mRNA in the chronic gastric cancer patients PBMC and stomach biopsy was detected by Real-time PCR,which represent their logcDNA/logGAPDH final mRNA level;the expression of CXCL8, CXCR1, CXCR2in gastric biopsy was observed by SP immunohistochemical staining.Results:IL-8in peripheral blood of patients with gastric cancer and its receptor CXCR1and CXCR2level significantly higher than the control group,HP (+) of IL-8and its receptor CXCR1and CXCR2compared with HP (-) group increased.Gastric biopsies of patients with IL-8and its receptor CXCR1and CXCR2level compared with the control group was significantly higher,cagA (+) of IL-8and its receptor CXCR1and CXCR2compared with cagA (-) group increased,vacA (+) of IL-8and its receptor CXCR1and CXCR2level compared with vacA (-) group increased.IL-8and IL-8mRNA and its receptor CXCR1, CXCR2mRNA in gastric cancer group was significantly associated with cagA(r=0.8659, P<0.01; r=0.0449, P<0.05; r=0.6955, P<0.01; r=0.7955, P<0.01);IL-8and its mRNA in chronic gastritis with cagA significant correlation (r=0.7041, P<0.01; r=0.1964, P<0.01), but CXCR1, CXCR2mRNA with the cagA no significant correlation (r=0.0776, P>0.05; r=0.0942, P>0.05); IL-8and its mRNA in gastric ulcer and cagA significant correlation (r=0.5877, P<0.01; r=0.1326, P<0.05), but CXCR1, CXCR2and cagA no significant correlation (r=0.0219, P>0.05; r=0.0040, P>0.05). IL-8and its IL-8mRNA and its receptor CXCR1, CXCR2mRNA in gastric cancer group and vacA significant correlation (r=0.8659, P <0.01; r=0.0515, P<0.05; r=0.7186, P<0.01; r=0.6932, P<0.01); chronic gastritis group IL-8and its mRNA and vacA significant correlation (r=0.7043, P<0.01; r=0.1273, P<0.05), but CXCR1, CXCR2and vacA no significant correlation (r=0.0334, P>0.05; r=0.0454, P>0.05); gastric ulcer IL-8and its mRNA with the vacA significantly related (r=0.5879, P<0.01; r=0.1604, P<0.05), but CXCR1, CXCR2mRNA and vacA no significant correlation (r=0.0544, P>0.05; r=0.0002, P>0.05).There was significantly correlation between IL-8mRNA and its receptor CXCR1, CXCR2mRNA in gastric cancer group and angiogenesis(r=0.7411, P<0.01;r=0.7454, P<0.01; r=0.7435, P<0.01).There was no difference between the intestinal-type gastric cancer and diffuse-type gastric cancer group increased significantly compared with the control group, the level of angiogenesis, the difference was statistically significant (P <0.01).There was significantly correlation between IL-8mRNA of intestinal type gastric cancer group and its receptors CXCR1, CXCR2and angiogenesis(r=0.7531, P <0.01; r=0.7531, P<0.01; r=0.7545, P<0.01). And there was also significantly correlation between diffuse gastric cancer group IL-8mRNA and its receptor CXCR1, CXCR2and angiogenesis(r=0.7944, P<0.01; r=0.7981, P<0.01; r=0.7971, P<0.01).Conclusions:The levels of IL-8in patients with gastric cancer were increased,and level of IL-8and its receptor CXCR1of CXCR2in the local lesion biopsies was significantly elevated, and which was positively correlated with the expression of cagA and vacA.Helicobacter pylori induce a variety of immune cells to release inflammatory cytokines such as IL-8by two key virulence factors with vacA and cagA,chemotaxis of neutrophils,monocytes to local lesion induced by chronic inflammation,promote gastric cancer(diffuse type and intestinal type). IL-8as a chemical-inducible factor recruiting neutrophils and macrophages and other immune cells in gastric cancer and the surrounding area,involved in the inflammatory damage.IL-8as a vascular endothelial growth factor,regulate gastric blood supply, promote angiogenesis of gastric cancer, promote endothelial cell differentiation, induce tumor cell migration.IL-8as a pro-mitotic factor, direct effects on gastric cancer cells,promote tumor cell growth and metastases leave primary microenvironment can still survive and grow.IL-8as a transfer factor,induce gastric cancer cell migration to promote tumor invasion of adjacent tissue and other parts of the transfer.CXCR1and CXCR2in gastric cancer tissue and vascular endothelial cells of gastric cancer and its combined with IL-8,not only activate the subsequent cascade signal conduction,also jointly participate in the occurrence,development,invasion and metastasis of gastric cancer.