The Role of Chemokine Receptor CXCR7 in Lung Cancer

OBJECTIVE To investigate whether CXCL12 and its receptor, CXCR7, play a role in lung cancer invasion and metastasis. METHODS Western blot and immunocytochemistry were used to detect CXCR7 protein expression in 8 lung cancer cell lines, EKVX, HOP62, HOP92, NCI-H23, NCI-H226, NCI- H322M, NCI-H446, and A549, and cell migration experiment was conducted to observe mobility of the lung cancer cells. The concentration of intracellular calcium in cytoplasm was measured under the fluorescence microscopy. RESULTS CXCR7 protein was positively expressed in the 8 lung cancer cell lines EKVX, HOP62, HOP92, NCI-H23, NCI-H226, NCI- H322M, NCI-H446, and A549. Following CXCL12 stimulation, obvious pseudopodia of lung cancer cells was observed under the microscope. The cell migration experiment showed that after incubation with CXCL12, the number of EKVX cells, which passed through the polycarbonate microporous filter membranes increased to a great extent. This phenomenon can be reversed by CXCR7-siRNA. After CXCL12 incubation, the intracellular Ca2＋ level in the EKVX cells was increased to a great extent. CONCLUSION Chemokine CXCL12 facilitates the migration of lung cancer cells by changing the concentration of intracellular Ca2＋. The CXCL12-CXCR7 axis may play an important role in lung cancer invasion and metastasis. It could be a potential target for lung cancer therapy and an effective way to prevent recurrence and metastasis of lung cancer.

The role of CXCL chemokine family in the development and prognosis of colorectal cancer

Objective:Colorectal cancer(CRC)is a major cause of cancer-related deaths worldwide.The class of chemokines known as cysteine-x-cysteine(CXC)motif ligands(CXCL)is thought to have a significant role in inflammation.A previous study implicated that CXCL family may play a role in angiogenesis and tumor development.In this comprehensive study,16 CXCLs in CRC will be analyzed for their prognostic values and expression patterns.Methods:To investigate CXCLs expression,immune cell infiltration,prognostic value significance,and genetic alteration among CRC patients,Gene Expression Profiling Interactive Analysis 2(GEPIA2),Kaplan-Meier plotter(K-M plotter),Gene Set Cancer Analysis(GSCA),STRING,GeneMANIA,and Sangerbox3.0 were employed.Results:As a result of our study,there was a significant increase in the levels of CXCL1/2/3/4/5/8/9/10/11/13/14/16 in CRC tissues,whereas CXCL12 was reduced.The expression of CXCL1/2/3/9/10/11 in CRC was linked to tumor stage.High expression of CXCL2/3/14 was associated with longer overall survival(OS)in colon adenocarcinoma(COAD)patients,and the overexpression of CXCL2/6/9/11/13 was related to long OS in rectum adenocarcinoma(READ)patients.Additionally,patients with CRC who expressed high levels of CXCL9/10/11 tended to have a longer disease-free survival(DFS).Furthermore,the functions of differentially expressed CXCLs were mainly involved in cytokine activity and chemokine effects.A significant correlation has been found between CXCLs expression and the infiltration of diverse immune cells in COAD and READ,including six types of CD4+T cells,macrophages,neutrophils,B cells,CD8+T cells,and dendritic cells.Conclusions:According to our study,CXCLs may not only serve as prognostic markers for CRC patients but also affect the immune status of CRC tissues,thereby providing new ideas for immunotherapy.

Chemokine stromal cell-derived factor 1/CXCL12 increases homing of mesenchymal stem cells to injured myocardium and neovascularization following myocardial infarction

Background Heart failure due to ischemic heart disease is still a major health problem. Myocardium regeneration emerges as a novel therapeutic method for treating myocardial infarction （MI）. However, it is affected by many factors. The present study was aimed to investigate the effect of chemokine stromal cell-derived factor 1 （SDF-1）/CXCL12 on mesenchymal stem cells （MSCs） homing to injured myocardium in a rat myocardial infarction model. Methods A rat myocardial infarction model was established by permanent left anterior descending branch ligation. Mesenchymal stem cells from donor rats were cultured in IMDM and labeled with bromodeoxyuridine. The rats were divided into two groups. SDF-1 expression was measured by in situ hybridization and immunohistochemistry in the sham operated or infarcted hearts at 1, 2, 4, 7, 14 and 28 days post operation in the SDF-1 detection group. The rats in the intervention groups were injected with SDF-1, anti-SDF-1 antibody or saline 4 days after myocardial infarction. Then, a total of 5×10^6 cells in 2.5 ml of phosphate-buffered saline were injected through the tail vein. The number of the labeled MSCs in the infarcted hearts was counted on the 3rd day post injection. Cardiac function and blood vessel density were assessed on the 28th day post injection. Results Self-generating SDF-1 expression was increased at the first day post MI, peaked at the 7th day and decreased thereafter while it remained unchanged in sham operated hearts. The MSCs enrichment in the host hearts were more abundant in the MI groups than in the non-MI group （P=0.000）; the MSCs enrichment in the host hearts were more abundant in the SDF-1 injected group than in the anti-SDF-1 antibody and saline injected groups （P = 0.000）. Cardiac function was improved more in the SDF-1 injected group than in the anti-SDF-1 antibody and saline injected groups （P = 0.000）. Neovascularization in the SDF-1 injected group increased significantly compared to the other groups （P= 0.000）. Conclusion Myocardial SDF-1 expression was increased only in the early phase post MI. SDF-1 may enhance MSCs homing to the injured heart and improve cardiac function by promoting neovascularization. Chin Med J 2009; 122（2）： 183-187