The value and association of CC chemokine receptor 7 expression in non-small cell lung cancer with lymph nodes metastasis

Objective： The aim of this study was to analyze the expression of CC chemokine receptor 7 （CCR7） in pulmonary tumor tissue and metastasized lymph nodes of non-small cell lung cancer （NSCLC）, explore the relationship between the expressions of CCR7 in pulmonary tumor tissue and metastasized lymph nodes, and discuss the significance. Methods： SABC immunohistochemical staining was used to investigate the expression of CCR7 by rabbit anti-human CCR7 monoclonal antibody, and the specimens were 17 cases of adenocarcinoma, 17 cases of squamous cell carcinoma, 12 cases of adenosquamous carcinoma, 4 cases of large cell carcinoma and 28 cases of metastasized lymph nodes of lung cancer. Negative control sections used 5 cases of inflammatory pseudotumor and 20 cases of normal lung tissue. Two independent pathologists observed all the specimens in the high power field （x 400） of microscope by double blind method. Results： （1） The expression of CCR7 in pulmonary tumor tissue was stronger than normal lung tissue （P 〈 0.005）; （2） The expressions of CCR7 in pulmonary tumor tissues and metastasized lymph nodes had no significant differences （P = 0.177）; （3） The expression of CCR7 had correlation with lymph nodes metastasis, and the expression in lymph nodes metastasis group was more than that of no lymph nodes metastasis group （P = 0.016）; （4） Along with the increment of clinical stage, the CCR7 expression had a tendency to increase （P = 0.003）. Conclusion： CCR7 has rich expression in carcinoma cell nests and lymph node metastasis. It demonstrates that CCR7 may be related to the development of lymph node metastasis in NSCLC.

Functions and mechanisms of chemokine receptor 7 in tumors of the digestive system

Chemokine(C-X-C motif)receptor 7(CXCR7),recently termed ACKR3,belongs to the G protein-coupled cell surface receptor family,binds to stromal cellderived factor-1[SDF-1,or chemokine(C-X-C motif)ligand 12]or chemokine(CX-C motif)ligand 11,and is the most common chemokine receptor expressed in a variety of cancer cells.SDF-1 binds to its receptor chemokine(C-X-C motif)receptor 4(CXCR4)and regulates cell proliferation,survival,angiogenesis and migration.In recent years,another new receptor for SDF-1,CXCR7,has been discovered,and CXCR7 has also been found to be expressed in a variety of tumor cells and tumor-related vascular endothelial cells.Many studies have shown that CXCR7 can promote the growth and metastasis of a variety of malignant tumor cells.Unlike CXCR4,CXCR7 exhibits a slight modification in the DRYLAIV motif and does not induce intracellular Ca^2+release following ligand binding,which is essential for recruiting and activating G proteins.CXCR7 is generally thought to work in three ways:(1)Recruitingβ-arrestin 2;(2)Heterodimerizing with CXCR4;and(3)Acting as a“scavenger”of SDF-1,thus lowering the level of SDF-1 to weaken the activity of CXCR4.In the present review,the expression and role of CXCR7,as well as its prognosis in cancers of the digestive system,were investigated.

CCR7/p-ERK1/2/VEGF signaling promotes retinal neovascularization in a mouse model of oxygen-induced retinopathy

AIM： To investigate the role of CCR7/p-ERKI/2/VEGF signaling in the mouse model of oxygen-induced retinopathy （OIR）. METHODS： Neonatal C57BL/6J mice were evenly randomized into four groups： normoxia, OIR, OIR control （treated with scramble siRNA）, and OIR treated （treated with CCR7 siRNA）. Normoxia group was not specially handled. Postnatal day 7 （P7） mice in the OIR group were exposed to 75%±5% oxygen for 5d （P7-P12） and then maintained under normoxic conditions for 5d （P12-P17）. Mice in the OIR control and OIR treated groups were given injections of scramble or CCR7 siRNA plasmid on P12 before returning to normoxic conditions for 5d （P12-P17）. Retina samples were collected from all mice on P17, stained with adenosine diphosphatase （ADPase）, and retinal neovascularization （RNV） was assessed. Retinas were also stained with hematoxylin and eosin （H＆E） for RNV quantitation. The distribution and expression of CCR7, p-ERKI/2 and vas- cular endothelial growth factor （VEGF） were assessed via immunohistochemistry, Western blot, and quantitative real-time polymerase chain reaction （qRT-PCR）. RESULTS： High oxygen promoted retinal neovascularization （P〈0.05） and increased the number of endothelial nuclei in new vessels extending from the retina to the vitreous body; CCR7 promoted this process （P〈0.05）. CCR7 and VEGF mRNA were expressed at higher levels in the OIR and OIR control groups than in the normoxia and OIR treated groups. CCR7, p-ERK1/2, and VEGF protein were expressed in the retinas of mice in the OIR and OIR control groups. Intravitreal injection of CCR7 siRNA significantly reduced CCR7, p-ERKI/2, and VEGF expression in the OIR mouse model （all P〈0.05）. CCR7 significantly enhancedthe neovascularization and non-perfusion areas in the OIR group （P〈0,05）, CCR7 siRNA significantly reduced levels of p-ERK1/2 and VEGF as compared to OIR controls （P〈0.05）. CONCLUSION： These results suggest that CCR7/p-ERK I/2NEGF signaling plays an important role in OIR, CCR7 may be a potential target for the prevention and treatment of retinopathy of prematurity.

Effect of CO2 pneumoperitoneum on the expression of the chemokine receptors CXCR4 and CCR7 in colorectal carcinoma cells in vitro

Background The ability of pneumoperitoneum in laparoscopic surgery to promote proliferation and metastasis of colorectal cancer has become a focus of research in the field of minimally invasive surgery. The aim of this research was to investigate the effect of CO~ pneumoperitoneum under different pressures and exposed times on the expression of chemokine receptors in colorectal carcinoma cells. Methods We constructed an in vitro pneumoperitoneum model. SW480 colon carcinoma cells were exposed to CO2 pneumoperitoneum under different pressures （6, 9, 12, and 15 mmHg） for 1, 2, and 4 hours. These cells were then cultivated under the same conditions as normal SW480 colon carcinoma cells without CO= pneumoperitoneum （control group）, treated at 37℃, and 5% CO2. The expression of the chemokine receptors CXC receptor 4 （CXCR4） and chemokine C receptor 7 （CCR7） was detected by immunocytochemistry and reverse transcriptase polymerase chain reaction after being cultivated for 0, 24, 48, and 72 hours. Results Immunocytochemistry showed that CXCR4 expression in SW480 cells was significantly decreased in the 6, 9, 12, and 15 mmHg CO2 pneumoperitoneum-treated groups for the same exposure times compared with controls （P 〈0.05）. CCR7 expression in SW480 cells was significantly decreased in the 12 and 15 mmHg CO2 pneumoperitoneum- treated groups compared with controls （P 〈0.05）. CXCR4 and CCR7 expression increased up to the level of the control group after 24 and 48 hours （P 〉0.05）. If the CO2 pneumoperitoneum pressure increased, CXCR4 and CCR7 expression decreased at all exposure times. If the CO2 pneumoperitoneum exposure time prolonged, there were no significant differences in CXCR4 and CCR7 expression under the same pressure. Under all exposure times, CXCR4 and CCR7 mRNA expression was significantly decreased in the 6, 9, 12, and 15 mmHg CO2 pneumoperitoneum-treated groups （P 〈0.05） compared with controls, and it increased up to the level of controls after being cultivated for 48 hours （P 〉0.05）. If the CO2 pneumoperitoneum pressure increased （with all exposure times） and exposure time prolonged （under the same pressure）, there were no significant differences in CXCR4 and CCR7 expression. Conclusions CXCR4 and CCR7 expression is temporarily affected after continuous CO2 pneumoperitoneum treatment. The high pressure of CO2 pneumoperitoneum plays an important role in suppressing the expression of these chemokine receptors. Different lengths of time of exposure to a CO2 pneumoperitoneum-like environment do not change CXCR4 and CCR7 expression.

Dendritic cell migration in inflammation and immunity

Dendritic cells(DCs)are the key link between innate immunity and adaptive immunity and play crucial roles in both the promotion of immune defense and the maintenance of immune tolerance.The trafficking of distinct DC subsets across lymphoid and nonlymphoid tissues is essential for DC-dependent activation and regulation of inflammation and immunity.DC chemotaxis and migration are triggered by interactions between chemokines and their receptors and regulated by multiple intracellular mechanisms,such as protein modification,epigenetic reprogramming,metabolic remodeling,and cytoskeletal rearrangement,in a tissue-specific manner.Dysregulation of DC migration may lead to abnormal positioning or activation of DCs,resulting in an imbalance of immune responses and even immune pathologies,including autoimmune responses,infectious diseases,allergic diseases and tumors.New strategies targeting the migration of distinct DC subsets are being explored for the treatment of inflammatory and infectious diseases and the development of novel DC-based vaccines.In this review,we will discuss the migratory routes and immunological consequences of distinct DC subsets,the molecular basis and regulatory mechanisms of migratory signaling in DCs,and the association of DC migration with the pathogenesis of autoimmune and infectious diseases.