The study on biological effects of SDF-1/CXCR4 axis composed of stromal cell derived factor-1 (SDF-1) and its receptor CXCR4 is progressing rapidly in the recent years. The SDF-1/CXCR4 axis plays an important role in occurrence and development of tumors and closely correlate with angiogenesis of tumors. This review focuses the progress of study on SDF-1/CXCR4 axis and angiogenesis in leukemia including SDF-1/ and its receptor CXCR4, the expression of SDF-1/CXCR4 axis in leukemic cells, the mechanism of relation between SDF-1/CXCR4 axis and angiogenesis in leukemia, the application of inhibitors against SDF-1/CXCR4 in treatment of angiogenesis and so on.
Chemokine CXCL12 ; metabolism ; physiology ; Humans ; Leukemia ; metabolism ; Neovascularization, Pathologic ; Receptors, CXCR4 ; metabolism ; physiology

Multiple myeloma (MM) is a plasma cell malignancy characterized by the high capacity to induce bone destruction. Osteolytic bone lesions in MM patients mainly result from an increased bone resorption related to the stimulation of osteoclast recruitment and activity. SDF-1a would represent a potential role and may provide a suitable therapeutic target for MM-mediated osteolysis. In this article the structure of SDF-1/CXCR4, the expression of SDF-1/CXCR4 in bone microenvironment of MM patients and its effect on osteoclasts, relation of SDF-1/CXCR expression with osteolytic bone lesions and prognosis of MM, SDF-1/CXCR4 as potential target for treatment of myeloma-osteopathia were reviewed.
Chemokine CXCL12 ; metabolism ; physiology ; Humans ; Multiple Myeloma ; complications ; metabolism ; Osteolysis ; etiology ; Receptors, CXCR4 ; metabolism ; physiology

Animals ; Cell Proliferation ; Chemokine CXCL12 ; metabolism ; Hepatocytes ; cytology ; metabolism ; Male ; Rats ; Rats, Wistar ; Receptors, CXCR4 ; metabolism

BACKGROUNDThe 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 CO2 pneumoperitoneum under different pressures and exposed times on the expression of chemokine receptors in colorectal carcinoma cells.

METHODSWe 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 CO2 pneumoperitoneum (control group), treated at 37°C, 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.

RESULTSImmunocytochemistry 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.

CONCLUSIONSCXCR4 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.

Carbon Dioxide ; adverse effects ; Cell Line, Tumor ; Colorectal Neoplasms ; metabolism ; Humans ; Receptors, CCR7 ; metabolism ; Receptors, CXCR4 ; metabolism ; Retropneumoperitoneum ; complications ; metabolism

The aim of this study was to explore the effects of the stromal cell-derived factor (SDF-1) and chemokine receptors (CXCR4) on chemotaxis of cord blood AC133(+) cells. The optimal SDF-1 concentration was determined in Transwell System. The cell migration was calculated from the number of cells passing through polycarbonate membrane with 8 microm pore. The expressions of CXCR4 in fresh and cultured cord blood AC133(+) cells were analyzed by flow cytometry with two-color direct immunofluorescence. The results showed that the chemotactic rate of fresh cord blood AC133(+) cells increased along with increasing concentrations of SDF-1, however, it tended to be stable when the concentration of SDF-1 reached 150 ng/ml. There was no difference in the chemotactic rate of cord blood AC133(+) cells between the group with SDF-1 adding CXCR4-blocking antibody and the group without SDF-1. When AC133(+) cells were cultured in vitro with hemopoietic growth factors, the expression of CXCR4 increased at the early stage, but decreased gradually along with time extending. In conclusion, there was correlation between the chemotactic rate of AC133(+) cells and the expression of chemokine receptor CXCR4.
Cell Line ; Chemokine CXCL12 ; pharmacology ; Chemotaxis ; Fetal Blood ; cytology ; Humans ; Receptors, CXCR4 ; metabolism ; Stromal Cells ; metabolism

OBJECTIVE: To explore the improvement effect of CXC chemokine receptor 4 (Cxcr4) gene-modified bone marrow mesenchymal stem cell (BMSC)-derived exosomes on aplastic anemia (AA), and make a preliminary exploration of the mechanism. METHODS: Mouse BMSCs were isolated and cultured, then infected by recombinant lentivirus carrying Cxcr4 gene. The expression of green fluorescence was observed through fluorescence microscope, the expression of Cxcr4 mRNA was detected by real-time fluorescence quantitative PCR, and the BMSC-derived exosomes modified with Cxcr4 gene were extracted. Mouse models of AA were constructed, and control group, model group (AA), AA+BMSC group, AA+NC-BMSC group, AA+Cxcr4-BMSC group were set up. Except control group and model group, the other three groups of mice were injected 400 μl exosomes from different sources via the tail vein, after 2 weeks, the routine blood indices and the number of bone marrow nucleated cells were detected, the pathological changes of bone marrow were observed by HE staining, and the expression level of Treg cells was detected by flow cytometry. RESULTS: Mouse BMSCs were successfully isolated, and BMSCs with high expression of Cxcr4 and their exosomes were obtained. Compared with the control group, the number of red blood cell (RBC), white blood cell (WBC), and platelet (PLT), the hemoglobin (Hb) content and proportion of Treg cells in the peripheral blood of mice in the model group significantly decreased (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01). The proliferation level of nucleated cells was low, and the medullary cavity was filled with a large number of fat cells. Compared with the model group, the number of RBC, WBC, PLT, the Hb content and proportion of Treg cells in the peripheral blood of mice in the AA+BMSC group, AA+NC-BMSC group, and AA+Cxcr4-BMSC group significantly increased (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01), and pathological changes of bone marrow were improved. In addition, the number of RBC, WBC, PLT, the Hb content and proportion of Treg cells in the peripheral blood of mice in the AA+Cxcr4-BMSC group were significantly higher than those in the AA+BMSC group (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01). CONCLUSION Injection of Cxcr4 gene-modified BMSC-derived exosomes has a certain improvement effect on AA mice, and the mechanism may be related to an increase of the proportion of Treg cells.
Anemia, Aplastic/metabolism* ; Animals ; Bone Marrow Cells ; Exosomes/metabolism* ; Humans ; Mesenchymal Stem Cells ; Mice ; Receptors, CXCR4

OBJECTIVETo explore the expression patterns of the chemokine CXCL12 and its receptor CXCR4 in human sperm.

METHODSWe collected semen samples from 10 fertile men, performed density gradient centrifugation, and then determined the expressions of both CXCL12 and CXCR4 in the sperm by RT-PCR and immunofluorescence staining.

RESULTSRT-PCR revealed the mRNA expressions of CXCL12 (0.641 +/- 0.180) and CXCR4 (0.464 +/- 0.100) in the sperm. However, only CXCR4 rather than CXCL12 was expressed at the protein level, and the positive staining for CXCR4 was observed mainly in the posterior part of the acrosome.

CONCLUSIONCXCL12 and CXCR4 are involved as important molecules in regulating the function of human sperm.

Acrosome ; metabolism ; Centrifugation, Density Gradient ; Chemokine CXCL12 ; metabolism ; Humans ; Male ; Receptors, CXCR4 ; metabolism ; Signal Transduction ; Spermatozoa ; metabolism

This study was purposed to explore the correlation of CXCR4, CCR1, CCR2 expression with curative effect of multiple myeloma (MM). Flow cytometry was used to detect the expressions of CXCR4, CCR1, CCR2 on cell surface of bone marrow from 48 newly diagnosed MM patients. These patients were divided into two groups: one group with expression of chemokine receptor (group I) and another group without expression of chemokine receptor (group II). The group I was consisted of 34 patients, but 3 out of them could not be continuously followed up. The group II was consisted of 14 patients. The MM patients of 2 groups were treated with chemotherapeutic drugs for 3 and 6 months, the curative efficacy of 2 groups were compared. The results showed that after treating for 3 and 6 months the effective rates of group I and group II were 80.6% (25/31) vs 50% (7/14) and 83.9% (26/31) vs 50% (7/14) respectively, which suggested that curative efficacy of group I was better than that of group II (p < 0.05). It is concluded that CXCR4, CCR1, CCR2 may be used as indexes for evaluating curative effect of MM patients.
Adult ; Aged ; Aged, 80 and over ; Female ; Flow Cytometry ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; metabolism ; Receptors, CCR1 ; metabolism ; Receptors, CCR2 ; metabolism ; Receptors, CXCR4 ; metabolism ; Treatment Outcome

OBJECTIVETo investigate the expression of CXCL12, its receptor CXCR4 and its correlations with clinical pathology and lymphangiogenesis in pancreatic adenocarcinoma (PAC).

METHODSThe tissue samples were obtained from 30 patients with PAC by surgery between January 2005 and December 2007, which including PAC, the cancerous peripheral tissues, the normal pancreatic tissues and peripheral lymph nodes. The patients age ranged from 35 to 78 years old (median 57.2 years old). The expressions of CXCL12 and CXCR4 in these tissues were assayed by immunohistochemical staining, RT-PCR and fluorescence quantitative real-time PCR.

RESULTSIn the immunohistochemical staining, the CXCL12 protein mainly located in the normal pancreatic cell envelopes and/or cytolymphs. In the immunohistochemical staining, the CXCR4 protein mainly located in the cell envelopes and/or cytolymphs of PAC. The results of RT-PCR and fluorescence quantitative real-time PCR indicated that the expression levels of CXCR4 mRNA in PAC tissues, the cancerous peripheral tissues and peripheral lympho nodes were higher than that in the normal pancreatic tissues (P < 0.01). The MLVD in PAC were detected by morphometric analysis respectively. The level of MLVD in III-IV stages was higher than I-II stages of PAC (P < 0.01), and in these cases which had lymphatic metastasis, the level of MLVD significantly increased (P < 0.01). And there was no correlation between the differentiation and histology types of PAC (P > 0.05). There was 22 samples that the CXCR4 protein was positive, and among these samples the MLVD was higher than that in negative group of CXCR4 protein (P = 0.003).

CONCLUSIONSThe expression of CXCR4 was significantly associated with lymphatic metastasis of PAC, and the higher expression of CXCR4 in PAC tissues was significantly associated with lymphangiogenesis of PAC.

Adult ; Aged ; Chemokine CXCL12 ; metabolism ; Female ; Humans ; Lymphangiogenesis ; Lymphatic Metastasis ; Male ; Middle Aged ; Pancreatic Neoplasms ; metabolism ; pathology ; Receptors, CXCR4 ; metabolism

OBJECTIVEThis review focuses on the state-of-the-art of CXCL12/CXCR4 signaling axis in pancreatic cancer and its role in tumor progression.

DATA SOURCESRelevant articles published in English were identified by searching in Pubmed from 1997 to 2013, with keywords "CXCL12", "CXCR4" and "pancreatic cancer". Important references from selected articles were also retrieved.

STUDY SELECTIONArticles about CXCL12/CXCR4 signaling axis in pancreatic cancer and relevant mechanisms were selected.

RESULTSPancreatic cancer has been one of the most lethal human malignancies, with median survival less than one year and overall 5-year survival only 6%. Tumor cells from pancreatic cancer express high level of CXCR4. CXCL12, the ligand for CXCR4, is extensively secreted by neighboring stromal cells and other distant organs. CXCL12 primarily binds to CXCR4, induces intracellular signaling through several divergent pathways, which are involved in progression and metastasis of pancreatic cancer.

CONCLUSIONSCXCL12/CXCR4 signaling axis may play an important role in the communication between pancreatic cancer cells and their microenvironment, which may have effect on tumor proliferation, invasion, angiogenesis, metastasis and chemoresistance. CXCL12/CXCR4 signaling axis may serves as a novel therapeutic target for pancreatic cancer.

Chemokine CXCL12 ; genetics ; metabolism ; Humans ; Pancreatic Neoplasms ; genetics ; metabolism ; Receptors, CXCR4 ; genetics ; metabolism ; Signal Transduction ; genetics ; physiology