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

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

OBJECTIVETo study the promotion effect of stromal cell-derived factor 1 (SDF-1) on the migration of epidermal stem cells (ESC) in the healing process of frostbite-wound model ex vivo.

METHODSA three-dimensional model of full-thickness frostbite of skin was constructed (with slot-like wound) out of skin equivalent. The expression of SDF-1 in wound stroma was observed with immunohistochemistry staining on post injury days (PID) 3 and 7. The model frostbite wounds were divided into control group (treated with PBS 50 microL per wound), SDF-1 group (treated with 100 ng/mL SDF-1, 50 microL per wound), and AMD3100 group [treated with 100 ng/mL AMD3100 (50 microL per wound) for 30 minutes, and then SDF-1 50 microL was added per wound]. The redistribution of ESC around wound was observed.

RESULTSThe expression of SDF-1 in wound stroma increased gradually on PID 3 and 7. Compared with those in control and AMD3100 groups, there were more ESC and epithelial cell layers, and more integrin beta(1)-positive cells appeared at the basal layer of wound in SDF-1 group, and some of the positive cells migrated upward to epidermis.

CONCLUSIONSSDF-1 contributes to wound repair through promoting ESC to migrate toward and gather around wound edge. This may be one of the mechanisms of ESC participating in wound repair.

Cell Movement ; Chemokine CXCL12 ; metabolism ; Epidermis ; cytology ; Frostbite ; metabolism ; therapy ; Humans ; Stem Cells ; cytology ; Wound Healing

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

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

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

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

OBJECTIVE: To investigate the role of IL-17A in promoting the activation of lung fibroblasts and the secretion of chemokine CXCL12, and to explore the possible mechanism. METHODS: Lung tissues of BALB/c mice were collected after intraperitoneal injection of recombinant mouse IL-17A (rmIL-17A). Real-time RT-PCR and Western blotting were used to detect the expression levels of α-smooth muscle actin (α-SMA) and collagen I in lung tissues, and immunohistochemical staining and real-time RT-PCR were used to determine the expression of CXCL12. Normal mouse primary lung fibroblasts were isolated and cultured, and identified by immunofluorescence staining with optical microscopy. Cells and supernatant of culture medium were collected after stimulation with rmIL-17A at different concentrations. mRNA levels of α-SMA, collagen I, and CXCL12 in the cells were determined by real-time RT-PCR, and the levels of collagen I and CXCL12 in the supernatant of culture medium were determined by ELISA. RESULTS: The mRNA and protein levels of α-SMA and collagen I in the lung tissue of mice injected with rmIL-17A were significantly increased compared with the control group (all CONCLUSIONS s: IL-17A can promote the activation of lung fibroblasts and translation into myofibroblast. The secretion of collagen is increased, which promote the deposition of extracullular matrix, and leads to the occurrence and development of lung fibrosis. CXCL12, a chemokine secreted by activated fibroblasts, may be involved in this process.
Actins/genetics* ; Animals ; Cells, Cultured ; Chemokine CXCL12/metabolism* ; Fibroblasts/metabolism* ; Interleukin-17/pharmacology* ; Lung/metabolism* ; Mice ; Mice, Inbred BALB C

OBJECTIVES: This study aimed to investigate how naringenin (Nar) affected the anti-inflammatory, vascula-rization, and osteogenesis differentiation of human periodontal ligament stem cells (hPDLSCs) stimulated by lipopolysaccharide (LPS) and to preliminarily explore the underlying mechanism. METHODS: Cell-counting kit-8 (CCK8), cell scratch test, and Transwell assay were used to investigate the proliferation and migratory capabilities of hPDLSCs. Alkaline phosphatase (ALP) staining, alizarin red staining, lumen-formation assay, enzyme-linked immunosorbent assay, quantitative timed polymerase chain reaction, and Western blot were used to measure the expression of osteopontin (OPN), Runt-related transcription factor 2 (RUNX2), vascular endothlial growth factor (VEGF), basic fibroblast growth factor (bFGF), von Willebrand factor (vWF), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6. RESULTS: We observed that 10 μmol/L Nar could attenuate the inflammatory response of hPDLSCs stimulated by 10 μg/mL LPS and promoted their proliferation, migration, and vascularization differentiation. Furthermore, 0.1 μmol/L Nar could effectively restore the osteogenic differentiation of inflammatory hPDLSCs. The effects of Nar's anti-inflammatory and promotion of osteogenic differentiation significantly decreased and inflammatory vascularization differentiation increased after adding AMD3100 (a specific CXCR4 inhibitor). CONCLUSIONS Nar demonstrated the ability to promote the anti-inflammatory, vascularization, and osteogenic effects of hPDLSCs stimulated by LPS, and the ability was associated with the stromal cell-derived factor/C-X-C motif chemokine receptor 4 signaling axis.
Humans ; Anti-Inflammatory Agents/pharmacology* ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Chemokine CXCL12 ; Lipopolysaccharides/pharmacology* ; Osteogenesis ; Periodontal Ligament/metabolism* ; Receptors, Chemokine/metabolism* ; Stem Cells ; Interleukin-8/metabolism*