Objective To understand role of chemokines and their receptors in pathogenesis, progression, and metastasis of gastric cancer, and to provide a better approach for diagnosis and treatment of gastric cancer. Method The literatures about the relationship between chemokines and their receptors and gastric cancer were reviewed. Results There were about 50 various chemokines and their receptors abnormally expressed in the tumor microenvironment. The main types related gastric cancer were the CXC, CC and CX3C chemokines and their receptors, which could promote the proliferation, invasion, and metastasis of the gastric cancer through several pathways like mTOR pathway, JAK2-STAT3 pathway, etc.. Conclusions Chemokines and their receptors play an important role in occurrence and development of gastric cancer. Further studies on chemokines and their receptors will not only assist in early diagnosis of gastric cancer, as well as estimation of clinical prognosis, but also provide an intervention target for gastric cancer.
ObjectiveTo investigate the expressions and significance of chemokines factor receptors 4 (CXCR4) and chemokines factor receptors 7 (CXCR7) in gastric cancer tissues. MethodsSixty-five patients with gastric cancer who treated in our hospital from January 2011 to June 2013 were retrospectively collected as gastric cancer group, and 20 patients with gastric ulcer were retrospectively collected as control group at the same time. The expressions of CXCR4 and CXCR7 in gastric cancer tissues and normal gastric tissues were measured by immunohistochemistry, and then the relation-ship among expressions of CXCR4/CXCR7 in gastric cancer tissues and clinicopathological features of patients with gastric cancer was explored, as well as its effect on survival. ResultsPositive expression rates of CXCR4 and CXCR7 were identi-fied in 80.00% (52/65) and 84.62% (55/65) of the gastric cancer group, and 5.00% (1/20) and 10.00% (2/20) in control group respectively, and the positive expression rates of CXCR4 and CXCR7 in gastric cancer group were significantly higher than those of control group respectively (χ2=36.65, P<0.01; χ2=38.55, P<0.01). The positive expression rate of CXCR4 in gastric cancer tissues was related with degree of differentiation, T staging, and TNM staging (P<0.05), positive expression rate of CXCR4 in patients with poor differentiation, T3-4 staging, and TNM Ⅲ-Ⅳ staging were higher than corresponding patients with moderate/high degree of differentiation, T1-2 staging, and TNM Ⅰ-Ⅱ staging. The positive expression rate of CXCR7 in gastric cancer tissues was related with degree of differentiation, T staging, and N staging (P<0.05), positive expression rate of CXCR7 in patients with poor differentiation, T3-4 staging, and N1-3 staging were higher than corrsponding patients with moderate/high degree of differentiation, T1-2 staging, and N0 staging. The survival situation was worse in patients with positive expression of CXCR4 and CXCR7 than corresponding patients with negative expression (P=0.01, P=0.01) respectively. ConclusionsCXCR4 and CXCR7 are related to gastric cancer genesis and development. Furthermore, the expressions of CXCR4 and CXCR7 could be used as markers to predict prognosis of gastric cancer. The regulation of CXCR4/chemokine ligand 12 (CXCL12) axis and CXCR7/CXCL12 axis may provide a new targeted therapy for patients with gastric cancer.
ObjectiveTo study the expression of cytokine-induced neutrophil chemoattractant-1(CINC-1)in rats with transfusion-related acute lung injury(TRALI),explore its possible role in the pathogenesis of TRALI. MethodsSixty Sprague-Dawley rats were randomly divided into a normal control group with sham operation,a positive control group with ALI induced by intravenous infusion of lipopolysaccharide(5 mg/kg),and a TRALI group treated by intraperitoneal injection of LPS 2h before the transfusion of human plasma (1mL),a LPS control group treated by intraperitoneal injection of LPS 2h before the transfusion of normal saline(1mL).The reverse transcription-polymerase chain (RT-PCR)was used to detect CINC-1 mRNA.The level of CINC-1 in lung tissue homogenate was measured by ELISA.Morphological changes of the lung tissue were observed under light microscope.Myeloperoxidase (MPO)in lung homogenate and wet lung weight to dry lung weight ratio (W/D)were observed.The number of cells and the percentage of polymorphonuclear neutrophil (PMN)in Bronchoalveolar lavage fluid (BALF)were also compared. ResultsCompared with the normal control group and the LPS control group,the expression of CINC-1 protein and CINC-1 mRNA were increased significantly in lung of the positive control group and the TRALI group(P<0.05).The number of cells and the percentage of PMN in BALF of the TRALI group [(310.63±76.67)×106/L and (33.57±11.51)%] were significantly higher than those in BALF of the normal control group [(101.36±63.83)×106/L and (9.87±3.56)%](P<0.05).Tissue water content and MPO activity in the TRALI group were significantly higher than those in the normal control group (P<0.05). ConclusionExpression of CINC-1 protein and CINC-1 mRNA are increased in the rat lung with TRALI and PMN infiltration in lung tissue,which suggests CINC-1 participate in the process of the PMN and endothelial cell adhesion and may play an important role in the pathogeneses of TRALI.
Objective To investigate the expression of chemokine receptor CXCR7 and the relation between its expression and clinicopathologic characteristics in papillary thyroid carcinoma. Method The expressions of CXCR7 in 79 cases of papillary thyroid carcinoma and their paracancerous tissues，and 33 cases of benign thyroid lesion tissues were detected by immunohistochemistry. Results The positive expression rates of CXCR7 were 0（0/79），65.8%（52/79），and 30.3%（10/33） in the paracancerous tissues，papillary thyroid carcinoma tissues，and benign thyroid lesions tissues，respectively. The positive expression rate of CXCR7 in the papillary thyroid carcinoma tissues was significantly higher than that in the paracancerous tissues （P＜0.05） or benign thyroid lesion tissues（P＜0.05）. The expression of CXCR7 was correlated with lymph node metastasis （P＜0.05）. Conclusion CXCR7 might take part in tumorigenesis，progression，and lymph node metastasis of papillary thyroid carcinoma.
Objective To explore the effect of dendritic cells (DCs) allergized by K-ras mutant peptide on expressions of chemokines CCL19, CCL22, and cytoskeletal protein fascin-1. Methods DCs were derived from peripheral blood in the presence of granuloceyte/macrophage-colony stimulating factor, interleukin (IL) -4 in vitro. The DCs were collected on day 7 after culture, and were divided into non-K-ras mutant peptide group (addition of RPMI 1604 culture solution 50 μg/ml) and K-ras mutant peptide group (addition of K-ras mutant peptide 50 μg/ml). Phenotype was identified by flow cytometry. The morphological structure was observed by scanning and transmission electron microscopies, respectively. The expressions of IL-12, CCL19, and CCL22 were tested continuously by enzyme-linked immunosorbent assay (ELISA). The expression of cytoskeletal protein fascin-1 was determined by Western blot. Results ①The expressions of CD1a, CD80, and CD86 after loading K-ras mutant peptide were higher than that before loading K-ras mutant peptide (Plt;0.01). ②The DCs with petal-like and branch-like profections after loading were observed under scanning electron microscopy; The DCs with irregular shapes, branch-like or burr-like were showed under transmission electron microscopy. ③The expressions of IL-12, CCL19, and CCL22 in the Kras mutant peptide group were higher than those in the non-K-ras mutant peptide group at different times (6, 12, 24, and 48 h) after loading Kras mutant peptide (Plt;0.01). ④The expression of fascin-1 in the K-ras mutant peptide group was also higher than that in the non-K-ras mutant peptide group (Plt;0.01). Conclusion K-ras mutant peptide can promote DC to mature and improve the expression of chemokines and cytoskeletal protein which will strengthen DC migration.
Objective To study the expression and significance of CCR chemokine receptor-7 (CCR7) protein and vascular endothelial growth factor-D (VEGF-D) protein in the progression of breast cancer, including normal breast tissue, slight and moderate atypical hyperplasia, severe atypical hyperplasia and intraductal carcinoma in situ, as well as invasive ductal carcinoma. Methods Immunohistochemistry was used to detect the expression of CCR7 and VEGF-D protein in the nomal breast tissue (n=20), slight and moderate ductal atypical hyperplasia tissue (n=20), severe atypical hyperplasia and intraductal carcinoma in situ tissue, as well as invasive ductal breast carcinoma tissue (n=73). In addition, the D2-40 staining was also used to determine lymphatic microvessel density (LMVD). Meanwhile, the relationship between the expression of the two kinds of protein and clinicopathological factors/LMVD was analyzed by statistical analysis in breast cancer, and the correlation between expression of CCR7 protein and expression of VEGF-D protein was analyzed too. Results ①The positive rates of CCR7 protein (χ 2 =23.905，P<0.050) and VEGF-D protein (χ 2 =22.349，P<0.050) were gradually increased in the normal breast tissue group 〔CCR7 protein: 0 (0/20), VEGF-D protein: 5.0% (1/20)〕, slight and moderate atypical hyperplasia group 〔CCR7 protein: 5.0% (1/20), VEGF-D protein: 20.0% (4/20)〕, severe atypical hyperplasia and intraductal carcinoma in situ group 〔CCR7 protein: 30.0% (6/20), VEGF-D protein: 40.0% (8/20)〕, and invasive ductal carcinoma group 〔CCR7 protein: 47.9% (35/73), VEGF-D protein: 57.5% (42/73)〕. ②The LMVD value gradually increased in normal breast tissue group (2.00±1.02), slight and moderate atypical hyperplasia group (6.70± 3.48), severe atypical hyperplasia and intraductal carcinoma in situ group (9.01±2.13), as well as invasive ductal carcinoma group (16.32±4.07), there was significant difference between any 2 groups (P<0.050). ③The expressions of CCR7 protein and VEGF-D protein were correlated with clinical staging, histological grading, lymph node metastasis, and expression of human epidermal growth factor receptor-2 (HER-2) protein in patients with breast cancer (P<0.050), the higher positive rates of CCR7 and VEGF-D protein occurred in patients with higher histological grading, later clinical staging of Ⅲ+Ⅳ (compared with staging of Ⅰ+Ⅱ), lymph node metastasis (compared with no lymph node metastasis), and positive expression of HER-2 protein (compared with negative expression of HER-2 protein). The result indicated that LMVD value was related with expression of VEGF-D protein (r=0.623, P<0.010) in patients with breast cancer, but there was no correlation with expression of CCR7 protein (r=-0.303, P>0.050). Furthermore, there was weak positive correlation between expression of CCR7 protein and expression of VEGF-D protein in breast cancer (r=0.112, P<0.050). Conclusion The results strongly suggest that the expression levels of the VEGF-D protein and CCR7 protein indicate the potential of translation some extent, and they play an important role in the progression of breast cancer.
ObjectiveTo investigate the role of CXCL13 in the onset and development of knee osteoarthritis by observing and comparing the expression of CXCL13 between osteoarthritis and normal synovium. MethodsThe synovium samples were collected from 30 patients with osteoarthritis who received total knee replacement (osteoarthritis group), including 11 males and 19 females with an average age of 66.7 years (range, 62-76 years). The synovium samples were collected from 22 patients without osteoarthritis who underwent traumatic amputation (control group), including 15 males and 7 females with an average age of 51.3 years (range, 48-56 years). The NimbleGen microarray detection was used to defect differentially expressed genes; the immunohistochemistry staining, Western blot, and real-time quantitative PCR (qRT-PCR) were used to detect the expressions of CXCL13 mRNA and protein. ResultsThere were 451 up-regulated genes and 810 down-regulated genes in the 22 885 genes which contained by mRNA gene chip, and CXCL13 gene expression was down-regulated. Immunohistochemistry staining and Western blot assay showed that the expression of CXCL13 protein was significantly lower in osteoarthritis group (0.408 0±0.101 8) than in control group (0.785 9±0.057 9) (t=15.630, P=0.000). qRT-PCR results showed that the expression of CXCL13 mRNA was significantly lower in osteoarthritis group (0.011 7±0.003 2) than in control group (1.041 4±0.129 7) (t=43.634, P=0.000). ConclusionLow expression of CXCL13 in the knee osteoarthritis synovium tissue may be associated with the onset and development of knee osteoarthritis.
Objective To investigate the effects of histone modification on the expression of chemokines in alveolar epithelial typeⅡ cells ( AECⅡ) in a rat model of chronic obstructive pulmonary disease ( COPD) . Methods 20 SD rats were randomly assigned to a normal control group and a COPD group. The rat model of COPD was established by cigarette smoking. Lung histological changes were observed by HE staining. AECⅡ cells were isolated and identified by alkaline phosphatase staining and electron microscopic. The mRNA expressions of monocyte chemoattractant protein ( MCP) -1, IL-8, and macrophage inflammatory protein ( MIP) -2αwere detected by real-time quantitative PCR. The expression of histone deacetylase ( HDAC) 2 was measured by western blot. Chromatin immunoprecipitation ( ChIP) was used todetect H3 and H4 acetylation, and H4K9 methylation in the promoter region of chemokine gene. Results Compared with the control group, the mRNA expressions of MCP-1, IL-8, and MIP-2αin the COPD group increased 4. 48,3. 14, and 2. 83 times, respectively. The expression of HDAC2 protein in the COPD group wassignificantly lower than in the control group ( 0. 25 ±0. 15 vs. 0. 66 ±0. 15, P lt; 0. 05) . The expression of HDAC2 had a negative correlation with the gene expressions of IL-8, MCP-1, and MIP-2α( r = - 0. 960,- 0. 914, - 0. 928, respectively, all P lt;0. 05) . The levels of H3 and H4 acetylation were higher, and H4K9 methylation level was lower in the promoter region of chemokine gene in the COPD group compared with the control group ( all P lt; 0. 05) . Conclusions MCP-1, IL-8, and MIP-2α participate and promote the lung inflammatory response in COPD. HDAC2-mediated histone modification may play an important role in COPD inflammation.
Objective To investigate the expression and clinical significance of CXCR4 in esophageal squamous cell carcinoma (ESCC). Methods Databases including PubMed, EMbase, Web of Science, CBM, VIP, CNKI and WanFang Data were searched from inception to April 2012, and the relevant references were also retrieved to collect relevant case-control studies. Two reviewers independently screened literature according to the inclusion and exclusion criteria, and evaluated the quality of the included studies. Then the meta-analysis was conducted using RevMan 5.1 software. Results A total of 5 case-control studies involving 493 ESCC tissues and 136 normal esophageal tissues were included. The results of the meta-analyses showed that, as for the positive rate of CXCR4 expression, it was higher in ESCC tissues rather than normal esophageal tissues (OR=12.03, 95%CI 6.76 to 21.44, Plt;0.000 01), in ESCC tissues with lymph node metastasis rather than those without lymph node metastasis (OR=4.35, 95%CI 2.48 to 7.62, Plt;0.000 01), as well as in moderate and low differentiated ESCC tissues rather than high differentiated ESCC tissues (OR=0.51, 95%CI 0.32 to 0.81, P=0.004); but no significant difference was found between the clinical stage I-II and clinical stage III-IV ESCC tissues. Conclusion The presently limited evidence shows CXCR4 expression is associated with ESCC, lymph node metastasis and degree of cell differentiation, indicating that CXCR4 may take a role in the whole course of carcinogenesis of ESCC. But the relationship between CXCR4 expression and clinical stage of ESCC is still unclear, which needs to be further proved by more large-scale, well-designed and high quality case-control studies.
Monocyte chemoattractant protein-1(MCP-1) is a cytokine which belongs to the CC chemokine family. Retinal pigment epithelium (RPE) cells, photoreceptors and microglial cells in the retina can secrete MCP-1. Physiological level of MCP-1 is important for preserving morphology of RPE and glial cells, as well as retinal function and gross morphology. MCP-1 is likely released from Müller glia and the RPE cells when retina under stress, and attracts microglia/macrophages to the sites of retinal damage, activates the microglia to ingest cell debris. MCP-1 has been found upregulated in the intraocular fluid of retina in patients and animal models with retinal detachment, posterior uveitis and age-related macular degeneration. The expression of MCP-1 may be response to retinal inflammation. Therefore, it is tempting to speculate that pharmacological targeting of MCP-1 may be a safe and viable strategy in treatment of retinal disease.