Correlation Between Chemokine Receptors CXCR4, CCR7 And Invasive Potential In Different Gastric Cell Lines

Background:Gastric cancer is one of the most common diagnosed malignancies in China,cancer metastasis is one of the important causes of death in patients with gastric cancer.The process of cancer metastasis is not random.Different cancer cells have their preferred homing sites. Recently, studies have increasingly shown that chemokines and their receptors play an important role in several aspects of tumor progression. Chemokines are a large family of chemotactic cytokines, which are fundamentally involved in the recruitment of leukocytes to specific tissues. Several studies have demonstrated that tumor cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Many observations indicate that, the CXCL12/CXCR4 and the CCL21/CCR7 chemokine ligand-receptor systems are common key mediators of tumor cell metastasis for several malignancies. Gastric cancer tend to metastasize to lymph node and peritoneum and there is no efficient therapy to treat this condition. A few previous studies demonstrated the high expression of CXCR4 and CCR7 in human gastric cancer and correlated with lymph node metastasis and clinicopathologic factors (differentiation, T stage, tumor recurrence, etc.)Objectives:In this study, we analyzed the expression of chemokine receptors CXCR4, CCR7 in human gastric carcinoma cell lines with different invasion ability and analyzed the relationship between the expression of CXCR4,CCR7 and the progression of gastric cancer. And then evaluated the probability of CXCR4, CCR7 as a molecular marker for diagnosis of gastric cancer progression and a therapy target.Methods:Expression of CXCR4 and CCR7 on MGC803, AGS, BGC823 and SGC7901 were analyzed by RT-PCR and Western blot, the invasion ability of four gastric cancer cell lines was measured using transwell chamber with matrigle.All the detection items in this study were repeated at least 3 times. Statistical analysis was done using SPSS software. The data was expressed as mean±SD. The Spearman correlation test was used to analyze expression levels of CXCR4, CCR7 and their invasive capacities in gastric cancer cell lines. P-value<0.05 was considered to be statistically significance.Results:Expression of CXCR4 mRNA on MGC803, AGS, BGC823 and SGC790 respectively was:1.2556±0.1384,0.7943±0.0913,0.4749±0.0744,0.2463±0344 expression of CCR7 mRNA respectively was:0.6071±0.1404,0.5355±0.0750,0.2549±0.0522,0.2466±0.0342.The protein expression of CXCR4 and CCR7 in four human gastric carcinoma cell lines showed a good agreement with mRNA expression. The penetrating cell number of MGC803, AGS, BGC823 and SGC790 were 400±18.2,310±4.0,110±13.9,85±9.5, respectively.The expression levels of CXCR4 in cancer cells showed a significant positive correlation with the invasive capacity (P<0.05). Conclusions:In this study, the data suggest that expression of CXCR4 is positively correlated with cell invasion phenotype in human gastric cancer cells and there is no differentiated expression of CCR7 in the four gastric cancer cell lines.