Objective To summarize the relationships between chemokines or chemokine receptors, especially CCL19/CCL21-CCR7 and CXCL12-CXCR4 axis and occurrence and development of gastric cancer. Methods Domestic and international publications online involving the relationships between chemokines, chemokine recepotors and gastric cancer in recent years were collected and reviewed. Results By regulating the microenvironment of the growth of gastric cancer, CCL19/CCL21-CCR7 played an important role in lymph node metastasis and CXCL12-CXCR4 axis played a key role in the development of peritoneal carcinomatosis. CCR7 might function as a specific prognostic marker for lymph node metastasis of gastric cancer. Blocking the CXCL12-CXCR4 axis might be useful for the future development of a more effective therapeutic strategy for gastric cancer involved in peritoneal dissemination. Conclusions Chemokines and chemokine receptors promote the evolution of gastric cancer in variable ways, so the mechanisms of which should be comprehended to provide a theoretical basis for the future treatment. As new therapeutic targets, chemokines and chemokine receptors have a prosperity for the clinic evaluation and treatment of gastric cancer.
ObjectiveTo detect the expressions of CD133 in four gastric cancer cell lines (KATO-Ⅲ, SGC7901, AGS, and MKN-45) and investigate the different biological characteristics of CD133 positive (CD133+) cells and CD133 negative (CD133-) cells in the KATO-Ⅲ cell lines. MethodsThe CD133 gene and protein expressions of four gastric cancer cell lines were evaluated by semiquantitative RT-PCR and Western blot, respectively. CD133+ cells in KATO-Ⅲ cell lines were isolated by magnetic activated cell sorting (MACS) and examined in morphology, growth characteristics, proliferation, and differentiation in vitro. The sensitivity of different concentrations (0.05, 0.10, 0.20, 0.50, and 1.00 mg/ml) 5-fluoropyrimidinedione (5-FU) were contrasted by drug sensitivity testing in vitro (Cell Counting Kit 8-assay) between CD133+ cells and CD133- cells. ResultsThe expressions of CD133 gene and protein in the KATO-Ⅲ cell lines were significantly higher than those in the other three cell lines (Plt;0.05). CD133+ cells produced spheroid colonies in serum-free medium culture and were ber abilities of proliferation and differentiation than those of CD133- cells in vitro. The inhibitor rate of the CD133+ cells at concentration of 0.50 mg/ml was lower than that of CD133- cells (Plt;0.05). ConclusionsCell population with CD133+ in the KATO-Ⅲ cell lines have b ability of cloning, better capability of proliferation and differentiation, as well as anticancer drug resistance to 5-FU. CD133 can be applied as one of surface markers for the detection to gastric cancer initiator cells.
Objective To investigate the prognostic value of epithelial-mesenchymal transition （EMT） related proteins （Snail， E-cadherin， and N-cadherin） in gastric cancer and its relationship with tumor initiating cells （TICs） marker （CD133）. Methods The expressions of EMT-related proteins and CD133 protein in the gastric cancer tissues and normal gastric mucosa tissues adjacent to gastric cancer were detected by Western blot method. The relations between the expressions of EMT-related factors proteins and CD133 protein and the clinicopathologic characters were analyzed. The correlations between EMT-related factors and CD133 were analyzed by Spearman. The correlations between EMT-related factors expressions and CD133 expression and survival were analyzed by Kaplan-Meier method and Log-rank test. Results ① The protein expression levels of Snail， N-cadherin， and CD133 in the gastric cancer tissues were significantly higher than those in the normal gastric mucosa tissues adjacent to gastric cancer （Snail：0.599±0.114 versus 0.259±0.108， P=0.020；N-cadherin：0.754±0.154 versus 0.329±0.134， P=0.001；CD133：0.635±0.119 versus 0.485±0.116， P=0.029）， while the protein expression level of E-cadherin was lower than that in the normal gastric mucosa tissues adjacent to gastric cancer （0.378±0.123 versus 0.752±0.156， P=0.003）.② The expression levels of Snail and N-cadherin in the gastric cancer patients with vascular invasion， lymphatic vessel invasion，N3 lymph node metastasis， diameter more than 5 cm， and Ⅲ＋Ⅳ staging were significantly higher than those in the patients without vascular invasion， lymphatic vessel invasion， N0-N2 lymph node metastasis， diameter less than 5 cm， andⅠ＋Ⅱ staging（P＜0.05）， while E-cadherin protein expression was lower than that in the patients without vascular invasion， lymphatic vessel invasion， N0-N2 lymph nodes metastasis， andⅠ＋Ⅱstaging （P＜0.05）. The expression levels of CD133 in the gastric cancer patients with lymphatic vessel invasion， diameter more than 5 cm， and Ⅲ＋Ⅳ staging were significantly higher than those in the patients without lymphatic vessel invasion， diameter less than 5 cm， andⅠ＋Ⅱ staging （P＜0.05）. ③The Snail and N-cadherin protein expressions were significantly positive correlated with CD133 protein expression， respectively （rs=0.278， P=0.048；rs=0.406， P=0.003）， while E-cadherin protein expression was significantly negative correlated with CD133 protein expression （rs=-0.504， P=0.000）.④ The survival time in the patients with lower expressions of Snail， N-cadherin， and CD133 were significantly longer than those in the patients with higher expressions of Snail， N-cadherin， and CD133 （P＜0.05）. The combination of Snail， N-cadherin， E-cadherin， and CD133 could effectively predict survival. Conclusions There is a significant correlation between EMT and gastric cancer TICs， and which are correlated with aggressive clinicopathologic features of gastric cancer. The combination of Snail， E-cadherin， N-cadherin， and CD133 may be effectively predict the prognosis of gastric cancer patients.
Objective To study the expression of CD133 mRNA in peripheral blood mononuclear cells （PBMCs） of patients with gastric adenocarcinoma （GC） before operation or after operation and its clinical significance. To learn the relationship of CD133 expressions in PBMCs to primary lesion of GC. Methods Fifty patients with GC，10 patients with gastric ulcer （GU）， and 10 healthy volunteers were registered in this research. Expressions of CD133 mRNA in PBMCs and in primary lesion of GC by semi-quantitative RT-PCR and expression of CD133 protein in primary lesion of GC by immunohistochemical staining were detected. Correlations of CD133 mRNA expression with clinicopathologic parameters and postoperative survival rate were analyzed. Relation between CD133 mRNA level and CD133 protein expression or lymphatic metastasis were assessed too. Results The brightness scale value （ABSV） of CD133 mRNA in PBMCs of the patients with GC before operation （0.270±0.163） was higher than that in the healthy volunteers （0.029±0.060） or in the patients with GU （0.059±0.099） （P=0.000）. The ABSV of CD133 mRNA in the PBMCs of patients with GC before operation was related to poor cell differentiation （P=0.002）， lymph vessel invasion （P=0.028），deeper tumor invasion （P=0.041），later lymph node metastasis stage （P=0.010），later TNM stage （P=0.006），and positive expression of CD133 protein in the primary lesion （P=0.011）. Relative analysis revealed that the ABSV of CD133 mRNA in the PBMCs of patients with GC before operation was related positively to metastatic lymphatic nodes ratio （rs=0.422，P=0.002），metastatic lymph node number （rs=0.398，P=0.004），and ABSV of CD133 mRNA in the primary lesion of GC （rs=0.337，P=0.017）. The ABSV of CD133 mRNA in the PBMCs of patients with GC after operation obtained from blood sample at 1 week after curative resection was higher than that in the patients before operation （P=0.021）. Patients suffered from deeper invasion inclined to have a higher ABSV of CD133 mRNA after surgery （P=0.039）. Higher expression of CD133 mRNA in patients after operation demonstrated a much poorer survival rate （P=0.013）. Conclusions Higher expressive level of CD133 mRNA in GC before operation is associated to poor cell differentiation，lymph vessel invasion，deeper invasion，higher lymph node metastasis，later TNM stage，and positive expression of CD133 protein. It is also related positively to metastatic lymphatic nodes ratio，metastatic lymph node number，and ABSV of CD133 mRNA in primary lesion of GC. The level of CD133 mRNA in PBMCs of patients with GC is higher after operation as compared with before operation，which demonstrates deeper invasion and poorer survival.