ABSTRACT
CCL20 and CCR6 are chemokines produced by a variety of cells. CCL20 and CCR6 combine to stimulate a series of downstream pathways, participate in the occurrence and development of various malignant tumors, and also play an important role in the invasion and metastasis of breast cancer and the process of chemotherapy resistance. Epithelial-mesenchymal transformation (EMT) is a key step in the process of tumor cell metastasis, which is characterized by loss of cell adhesion, down-regulation of E-cherherin expression, up-regulation of mesenchymal markers and fibrinectin expression, and enhancement of cell motor ability and invasion ability. This article reviews the research of CCL20-CCR6 biological axis and EMT on invasion and metastasis of breast cancer cells.
ABSTRACT
Objective To explore the expression and clinical significance of chemokine receptor 6 (CCR6)/chemokine ligand 20(CCL20) axis in hepatocellular carcinoma (HCC).Methods From March 2003 to December 2005,48 patients with HCC were selected,and one specimen of HCC tissue and one of corresponding adjacent tissue were taken from every patient.Another eight patients with benign liver lesions were selected,and one specimen of surgical sectioned normal liver tissue of each was taken.The relative expression quantity of CCR6 and CCL20 at mRNA level was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR).And the expression of CCR6 and CCL20 at protein level was determined by immunohistochemisty methods.One-way analysis of variance (ANOVA) was performed for comparison among groups of measurement data.Chi-square test was used for rate comparison.The correlation coefficient was calculated by Spearman's method.Survival curves were plotted by Kaplan-Meier method and the survival rate was compared by Log-rank test.Results The relative expression quantity of CCR6/CCL20 at mRNA level in HCC tissues (0.99±0.21 and 0.46± 0.11) were significantly higher than those of para carcinoma tissues (0.33 ± 0.09 and 0.31 ± 0.07) and normal liver tissues (0.22±0.06 and 0.28±0.05),and the differences were statistically significant (F=127.43 and 21.10,both P＜0.05).The positive percentage of CCR6 protein expression in HCC tissues (54.17％,26/48) was significantly higher than that in para carcinoma tissues (16.67％,8/48) and normal liver tissues (0/8),and the difference was statistically significant (x2 =19.55,P＜0.05).There was no statistically significant difference in the positive percentage of CCL20 protein expression among HCC tissues (50.00％,24/48),paracarcinoma tissues (33.33％,16/48),normal liver tissues (2/8) (all P＜0.05).There was correlation between the positive percentage of CCR6 protein expression and that of CCL20 protein expression in HCC tissues (r=0.42,P＜0.05).The positive percentage of CCR6 protein expression was correlated with the pTNM stage of HCC,vascular tumor thrombosis,intrahepatic metastasis and lung metastasis (x2 =5.48,4.02,5.07 and 5.19,all P＜0.05).The positive percentage of CCL20 expression was significantly correlated to tumor maximum diameter and pTNM stage (x2 =4.09 and 4.00,both P＜0.05).Both the disease-free survival (DFS) rate and overall survival (OS) rate of CCR6-positive group were significantly lower than those of negative group (x2 =4.57 and 6.57,both P＜ 0.05).There were no significant differences in DFS rate and OS rate between CCL20-positive group and negative group (both P＞0.05).Conclusion CCR6/CCL20 axis may be related with the malignant behavior and the prognosis of HCC.