ObjectiveTo investigate the expressions of chemokine receptor CXCR4 and CCR7 in thyroid cancer and its clinicopathologic significance. MethodsFifty-five patients with thyroid cancer were selected in the Affiliated Hospital of North Sichuan Medical College from 2006 to 2009, and 30 patients with thyroid adenoma were selected in the same hospital during 2009. The expressions of CXCR4 and CCR7 were detected in all the selected cases samples (including thyroid cancer and thyroid adenoma) by immunohistochemical SP technique. ResultsThe positive expression rates of CXCR4 and CCR7 in the thyroid cancer were higher than those in the thyroid adenoma (Plt;0.01), which in the thyroid cancer with clinical stage Ⅲ+Ⅳ were higher than those of the clinical stage Ⅰ+Ⅱ (Plt;0.05). The positive expression rate of CCR7 in the thyroid cancer with lymph node metastasis was higher than that of the thyroid cancer without lymph node metastasis (Plt;0.05), which of CXCR4 in the patients with thyroid cancer was independent of lymph node metastasis (Pgt;0.05), and which of CXCR4 and CCR7 were also independent of the age and gender of the patients with thyroid cancer (Pgt;0.05). The positive expressions of CCR7 and CXCR4 in all the patients with thyroid cancer was positively correlated (rs=0.491, P=0.000). ConclusionsCXCR4 and CCR7 are involved in the coordination of thyroid cancer progression. They can be used as prognostic indicators of thyroid cancer. High expression of CCR7 is prone to lymph node metastasis of thyroid cancer.
Objective To investigate the expressions of CXCR4 and β-catenin in pancreatic cancer, explore the relationship between them, and explore the possible biomarkers about invasion and metastasis of pancreatic cancer. Methods Forty-eight samples of pancreatic cancer and 20 samples of normal pancreas tissues were selected. The expressions of CXCR4 and β-catenin were examined by the immunohistological technique. Spearman, Chi-square， and rank test were used to analyze the relation between the protein expressions and clinical characteristics. Survival analysis was evaluated by Kaplan-Meier product limit method and Log-rank test. Variables were evaluated by Cox proportional hazards analysis. The size of test was 0.05. Results The positive expression rates of CXCR4 and β-catenin in pancreatic cancer tissues were 85.4% (41/48) and 75.0% (36/48), respectively. Co-expression rate of CXCR4 and β-catenin was 70.8% (34/48). There were significant differences between various CXCR4 staining and lymph node metastasis and TNM stage (P=0.012, 0.005, respectively). β-catenin positive expression was associated with lymph node metastasis (P=0.047). However, abnormal β-catenin positive expression could not determine the clinical survival. Kaplan-Meier estimated curves suggested that clinical prognosis was poor for patients with CXCR4 expression. Multivariate analysis showed that CXCR4, late TNM stage, and lymph node metastasis were independent prognostic factors for pancreatic cancer. Conclusions Both CXCR4 and β-catenin abnormally express in pancreatic cancer. CXCR4 may be an important marker for pancreatic cancer progression.
Objective To evaluate the effect of neoadjuvant chemotherapy on the expression of CXCR4 in breast cancer and its clinical significance.Methods The clinical data of 59 patients with breast cancer of stage Ⅱ and stage Ⅲ underwent neoadjuvant chemotherapy with paclitaxel plus epirubicin for 3 cycles between April 2005 and March 2009 were retrospectively analyzed. The expression of CXCR4 in the breast cancer tissues before and after neo-adjuvant chemotherapy was examined by immunohistochemistry and its relationship with clinicopathologic factors was analyzed.Results The CXCR4 positive expression was observed in 56 patients with breast cancer (94.9%), but not in corresponding nontumor normal tissues. The expression level of CXCR4 was correlated to lymph nodes metastasis (P=0.019) and breast cancer stage (P=0.040), but it was not correlated to age of patients, tumor size, grade, hormone receptor (ER and PR)， and HER2 status. The expression level of CXCR4 was significantly decreased after neoadjuvant chemotherapy. Decline extent of CXCR4 expression after chemotherapy and CXCR4 expression level were not correlated to the effect of neoadjuvant chemotherapy, while the effect of chemotherapy in patients expressed CXCR4 in cluster distribution was better than that in scattering distribution (P=0.015). Conclusion The decline extent of CXCR4 expression level after paclitaxel combined with epirubicin neoadjuvant chemotherapy is not correlated to the efficacy, but its expressing distribution may be considered as an index to the effect of neoadjuvant chemotherapy.
ObjectiveTo study the mechanism of invasion of CD133 positive population in gallbladder cancer. MethodsThe invasive abilities of the CD133 positive cells and the CD133 negative cells were detected by Transwell.The CXCR4 mRNA and protein in the CD133 positive cells and the CD133 negative cells were detected by the semi-quanti-tative RT-PCR, Western blot method, and immunofluorescence, respectively.SDF-1αand AMD3100 were respectively used to stimulate/inhibit the GBC-SD cells.The invasive ability and the migration force were detected in the CD133 posi-tive cells and the CD133 negative cells.The expressions CD133 mRNA and protein of the GBC-SD cells were detected by semi-quantitative RT-PCR and Western blot method, respectively. Results①The number of invasion cells in the CD133 positive cells was significantly more than that in the CD133 negative cells (23.78±8.74 versus 6.56±3.09, P=0.000 7).②The fluorescent protein of CXCR4 in the CD133 positive cells was stronger than that in the CD133 negative cells.The expression of CXCR4 mRNA in the CD133 positive cells was significantly higher than that in the CD133 negative cells (0.642 4±0.020 4 versus 0.335 9±0.043 2, P=0.004).The expression of CXCR4 protein in the CD133 positive cells was significantly higher than that in the CD133 negative cells (0.765 0±0.106 6 versus 0.409 4±0.019 5, P=0.013).③In the CD133 positive cells, compared with the control group, the number of invasion cells was significantly increased in the SDF-1αgroup (62.89±15.27 versus 23.78±8.74, P=0.000 6) and decreased in the AMD3100 group (10.33±2.00 versus 23.78±8.74, P=0.000 2).In the CD133 negative cells, compared with the control group, the number of invasion cells was not significant change in the SDF-1αgroup (6.89±4.23 versus 6.59±3.09, P=0.41) and in the AMD3100 group (6.11±2.67 versus 6.59±3.09, P=0.38), respectively.④In the CD133 positive cells, compared with the control group, the number of migration cells was significantly increased in the SDF-1αgroup (74.56±15.80 versus 35.56±10.97, P=0.000 3) and decreased in the AMD3100 group (12.67±2.40 versus 35.56±10.97, P=0.000 2).In the CD133 negative cells, compared with the control group, the number of migration cells was not significant change in the SDF-1αgroup (9.78±2.04 versus 9.56±1.74, P=0.43) and in the AMD3100 group (9.54±1.74 versus 9.56±1.74, P=0.42).⑤In the GBC-SD cells, compared with the control group, the CD133 mRNA was significantly increased in the SDF-1αgroup (0.626 5±0.048 7 versus 0.450 0±0.024 3, P=0.004) and decreased in the AMD3100 group (0.359 3±0.047 3 versus 0.450 0±0.024 3, P=0.011);the CD133 protein was significantly increased in the SDF-1αgroup (0.508 9±0.020 7 versus 0.440 9±0.013 0, P=0.016) and decreased in the AMD3100 group (0.317 7±0.013 7 versus 0.440 9±0.013 0, P=0.004). ConclusionThe high invasion ability of CD133 positive population in gallbladder cancer might be due to the high expression of CXCR4.
Mesenchymal stem cells (MSC) are considered to have important value in the treatment of various diseases because of their low immunogenicity, transferability, and strong tissue repair capacity. Stromal cell derived factor-1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) pathway plays an important role in migration of MSC. The induction of homing of MSC to retina by regulating SDF-1/CXCR4 may exert the curative effect on diabetic retinopathy to greatest exent.
ObjectiveTo investigate the effects of migration and expression from chemokine receptor 4 (chemokine receptor-4, CXCR4) of rat bone marrow mesenchymal stem cells (BMSCs) which were pretreated by atorvastatin (ATV) in vitro.MethodsIsolated, cultivated, identified the BMSCs, pretreated P4-P6 of BMSCs with different concentrations of ATV for 12 hours. The experimental group was divided into control group, 0.1 nM/L (group 0.1 nM), 1 nM/L (1 nM group), 10 nM/L (10 nM group), 100 nM/L (100 nM group), 1 000 nM/L (1 000 nM group). The mRNA and protein of CXCR4 were determined by real time-polymerase chain reaction and Western blot. Immunofluoreseence assay were used to detect the expression levels of CXCR4. The migration ability of BMSCs were measured by transwell chamber.ResultsImmunofluoreseence assay showed the protein level of CXCR4 of group 1 nM and 10 nM were significantly higher than the other group. RT-PCR and Western blot showed the protein and mRNA level of CXCR4 in 10 nM was higher than that in group 1 nM. The migration ability of group 10 nM was higher than 1 nM and control group.ConclusionsATV can be dose-dependent promote expression levels of CXCR4 of BMSCs cultivated in vitro.
ObjectiveTo systematically review the relationship between the expression of CXCL12/CXCR4 and pancreatic cancer.MethodsPubMed, EMbase, The Cochrane Library, Wiley Online Library, CNKI, VIP, WanFang Data and CBM databases were electronically searched to collect case-control studies on CXCL12/CXCR4 expression in pancreatic cancer from inception to February 1st 2020. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies; then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 21 case-control studies involving 1 677 cases and 1 690 controls were included. The results of meta-analysis showed that the expression of CXCR4 in pancreatic cancer tissue was higher than normal tissue (OR=21.40, 95%CI 5.70 to 80.31, P<0.01), in carcinoma of head of pancreas been higher than carcinoma of pancreatic body and tail, (OR=1.58, 95%CI 1.02 to 2.44, P=0.04), in pancreatic cancer with lymph node metastasis been higher than without lymph node metastasis (OR=3.14, 95%CI 1.98 to 4.99, P<0.01), in pancreatic cancer with high TNM stages (Ⅲ, Ⅳ) been higher than low TNM stages (Ⅰ, Ⅱ) (OR=3.67, 95%CI 1.98 to 6.81, P<0.01), in pancreatic cancer with distant metastasis been higher than without distant metastasis (OR=3.56, 95%CI 1.71 to 7.39, P<0.01), and in pancreatic cancer with vascular invasion was higher than without vascular invasion (OR=3.22, 95%CI 1.70 to 6.09, P<0.01). The expression of CXCR4 was not statistically correlated with age, gender, pancreatic cancer tissue and paracancerous tissue, pancreatic cancer tissue and paracancerous lymph nodes, differentiation degree. There was no statistical correlation between the expression of CXCL12 and the differentiation degree, and lymph node metastasis.ConclusionsIn pancreatic cancer, the high expression of CXCR4 is related to lymph node metastasis, high TNM stage, distant metastasis, vascular invasion indicate poor prognosis. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.
目的 检测血管内皮生长因子（VEGF）、白细胞分化抗原34（CD34）及CXC趋化因子受体4（CXCR4）在转移性鼻咽癌患者鼻咽部肿瘤组织中的表达，探讨它们与鼻咽癌各种临床病理因素的关系以及它们之间的相互联系。 方法 采用免疫组织化学链霉素抗生物素蛋白-过氧化物酶连结法检测2003年3月－2009年5月35例转移性鼻咽癌患者VEGF、CD34及CXCR4在鼻咽部肿瘤组织中的表达情况，结合患者临床病理特征进行分析。 结果 转移性鼻咽癌患者鼻咽部肿瘤组织中的VEGF及CXCR4阳性表达率分别为62.9%（22∕35）和42.9%（15∕35），CD34计数为11～92，平均43.2 ± 20.5。无肺转移较有肺转移的患者VEGF的阳性表达率高（78.9%、43.8%，P=0.043），多器官转移较单器官转移的患者CXCR4的表达强度高（62.5%、26.3%，P=0.044）。 结论 VEGF表达阳性的患者易发生肺转移；CXCR4强表达的患者易发生多器官转移。
ObjectiveBased on the rat in situ perfusion system, to explore the effect of up-regulating Chemokine (C-X-C motif) receptor 4 (CXCR4) expression on bone marrow neutrophils in modulating its ECC-related rapid release. MethodsTwelve SD rats were randomly divided into fucoidan perfusion group (F, n=6) and control group (C, n=6) after in situ perfusion system establishment. Rats in F group received perfusion of fucoidan solution (total volume 6 ml, 1 h) and C group received buffer only. Femurs from two groups were dissected after one-hour perfusion and bone marrow tissues were collected. The neutrophil CXCR4 expression in two groups were compared using flowcytometry. Eighteen SD rats were randomly divided into fucoidan perfusion group (F', n=6), fucoidan and AMD-3100 perfusion group (F+AMD3100, n=6) and control group (C', n=6) after in situ perfusion system establishment. Rats received desired interventions before stimulation from ECC plasma. After that, 40-min perfusions of buffer were added and total counts of neutrophil in perfusates were compared. ResultsThe percentages of CXCR4 (+) cell and CXCR4 expression fluorescence in F group were 4.71%±0.21% and 161.3±7.8 respectively while the values were 1.11%±0.11% and 58.4±6.5 respectively in C group. Values in F group were both significantly higher than those in C group (P<0.05). The total counts of neutrophil in perfusates from F' group, F+AMD3100 and C' group were 261 393.7±12 470.6, 872 635.2±10 430.6 and 818 675.2±10 708.8, respectively. Statistically differences were observed between each other (P<0.05). ConclusionBone marrow neutrophil CXCR4 expression of SD rat could be effectively up-regulated by perfusion of fucoidan within the in situ perfusion system. ECC-plasma-stimulated bone marrow neutrophil release in rat could be inhibited by fucoidan induced up-regulation of neutrophil CXCR4 expression, and this inhibition effect could be canceled by AMD-3100 intervention.