EDTA Enhances Stromal Cell–derived Factor 1α–induced Migration of Dental Pulp Cells by Up-regulating Chemokine Receptor 4 Expression
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The CXCR4/CXCL12 pathway has recently been reported to be involved in stimulating the metastasis of many different neoplasms, in which CXCR4 activates various phenomena such as chemotaxis, invasion, angiogenesis and proliferation. The purpose of this study was to analyze a possible association between the expression of chemokine receptors CXCR4, CCR6 and CCR7 with the clinicopathological features of cutaneous malignant melanoma, and to assess the usefulness of these chemokine receptors for diagnosis and prognosis. In our study, a percentage of immunoexpression of both CXCR4 and its ligands CXCL12 was associated with high clinical risk. In contrast, the patients with a low immunoexpression of CXCR4 and CXCL12 had low clinical risk. CCR6 and CCR7 immunoexpressions were also correlated with some clinical parameters, but seemed no more useful than CXCR4. These data suggest that the assessment of CXCR4 immunoexpression is a novel tool for predicting tumor aggressiveness in malignant melanomas, and in particular, a high immunoexpression percentage of CXCR4 and CXCL12 might be a sign of a poor prognosis.
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[Objective]To explore distribution of chemokine receptor CXCR4 on clear cell renal carcinoma. CXCR4 were stained on clear cell renal carcinoma samples with monoclonal antibody by immunohistochemistry and the results were statistically analyzed With their surgical,pathological and clinical data. All the samples were positively stained with CXCR4.They were divided into focal and diffuse groups based on the staining pattern and the diffuse group was divided into the high-expression and low-expression ones.The significant difference was found between focal and diffuse groups,high-expression and low-expression groups as well. [Conclusion] Expression of CXCR4 may be close related with prognosis and metastasis.
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Radiotherapy plays an important role in the treatment of malignant head and neck tumors. Chemokines are chemotactic cytokines, which can induce tumor proliferation as well as metastasis, although the influence of chemokines and their signaling pathways via chemokine receptors is not fully understood. Moreover, the radiation-induced expression of chemokines and chemokine receptors is poorly studied. Therefore, the purpose of this work was to analyze the expression of the chemokines of the CC-and CXC-class and their receptors in untreated and in irradiated squamous cell carcinoma of the head and neck (SCCHN). The expression of chemokines and chemokine receptors in 15 head and neck carcinoma cell lines and two normal tissue cell lines was analyzed. The spontaneous expression and the expression 6 hours after irradiation with 2 Gy was determined. To validate the results, certain chemokines and chemokine receptors were re-analyzed in selected cell lines. In this second independent analysis the expression was detected for 48 hours after irradiation. Gene expression of chemokines and their receptors was detected by real-time PCR. In addition, the protein expression of two chemokines was analyzed by ELISA. The results of the first analysis showed, that the chemokine receptors were less widely expressed in the investigated cell lines than the chemokines. Irradiation with 2 Gy caused an altered expression of the chemokines and chemokine receptors in all investigated cell lines. Radiation caused up- and downregulation in the expression of the chemokines, whereas the expression of the investigated receptors was predominantly downregulated after irradiation. The results of the chemokine expression were validated in the second, independent analysis. Radiation caused again up- and downregulation in the expression of the chemokines, but also showed that the expression of the chemokines and its receptors varies over the entire period of 48 hours after irradiation. The protein expression of the chemokines CXCL1 and CXCL12 corresponded well with the mRNA expression. In summary, irradiation of squamous cell carcinoma of the head and neck (SCCHN) and normal tissue cells caused a radiation-induced change of gene expression of the chemokine and its receptors. The results of this analysis show the complexity of the topic, so further studies will be needed to fully understand the influence of chemokines and chemokine receptors and their effect under a treatment of squamous cell carcinoma of the head and neck.
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In different tumour entities, expression of the chemokine receptor 4 (CXCR4) has been linked to tumour dissemination and poor prognosis. Therefore, we evaluated, if the expression of CXCR4 exerts similar effects in human hepatocellular carcinoma (HCC). Expression analysis and functional assays were performed in vitro to elucidate the impact of CXCL12 on human hepatoma cells lines. In addition, expression of CXCR4 was evaluated in 39 patients with HCC semiquantitatively and correlated with both, tumour and patients characteristics. Human HCC and hepatoma cell lines displayed variable intensities of CXCR4 expression. Loss of p53 function did not impact on CXCR4 expression. Exposure to CXCL12 mediated a perinuclear translocation of CXCR4 in Huh7/Hep3B cells and increased the invasive potential of Huh7 cells. In HCC patients, CXCR4 expression significantly correlated with progressed local tumours (T-status; P=0.006), lymphatic metastasis (N-status; P=0.005) and distant dissemination (M-status; P=0.009), as well as with a decreased 3-year-survival rate (P=0.01). In summary, strong expression of CXCR4 is significantly associated with progressed hepatocellular cancer.
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The chemokine receptors CCR5 and CXCR4 are the main coreceptors of the macrophage-tropic and T-cell- tropic HIV-1 strains, respectively. CCR5 antagonists (such as TAK-779 and SCH-C) and CXCR4 antagonists (such as AMD3100 and T22) can block HIV-1 entering their target cells by binding to CCR5 and CXCR4, respectively. The mechan- isms of HIV-1 binding to these two coreceptors and progress of research and development of the coreceptor antagonists are reviewed.
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