Collagen content and C-X-C motif chemokine ligand 12 expression in neoplastic breast stroma

SUMMARY OBJECTIVE: This study aimed to evaluate the expression of C-X-C motif chemokine ligand 12 and its C-X-C chemokine receptor type 4, and the tumor-stroma ratio using collagen stromal content of breast cancer samples, correlating it with clinicopathological data. METHODS: Through a retrospective cohort study, samples were obtained from female patients, over 18 years of age, with the disease in stages 1-4, who underwent mastectomy or lumpectomy. The biopsies were provided by the Oncology sector of the Hospital das Clínicas of Universidade Federal de Pernambuco, Recife city, in 2011-2014, including samples of invasive ductal carcinoma, ductal carcinoma in situ, or benign changes (fibroadenoma and hypertrophy), which were analyzed between 2020 and 2022 by immunohistochemistry for the expression of stromal cell characteristics. Collagen content was tested by Gomori staining and digital analysis of images. RESULTS: Absence of stromal expression of C-X-C motif chemokine ligand 12 was associated with longer disease-free survival (disease-free survival=0.481), and expression of C-X-C chemokine receptor type 4 was associated with lower disease-free survival. An association was observed between clinicopathological variables and stromal expression of chemokines, that is, an association of stromal C-X-C motif chemokine ligand 12 with histological grade, angiolymphatic invasion, and an association between C-X-C chemokine receptor type 4 expression and histological grade. Analyses of digital pixels images of collagen and tumor cells showed a lower percentage of collagen in the invasive ductal carcinoma samples (39%), unlike samples without neoplasms (78%). CONCLUSION: Low expression of C-X-C motif chemokine ligand 12 may be associated with a worse prognosis for breast cancer. Collagen staining analyzed using digital images represents an opportunity for clinical application and is indicative of the prognosis of the tumor microenvironment in breast carcinoma.

The relationship between MMP-2 rs243865, MMP-9 rs398242 and CXCL-12 rs1801157 gene polymorphisms with Japanese encephalitis disease and disease outcome in North Indian population

Background & objectives: Japanese encephalitis virus (JEV) is one of the most important causes of acute and uncontrolled inflammatory disease in Asia. Matrix metalloproteinases (MMPs) and chemokines play a detrimental role in the host response to JE disease, aetiology, and disease outcome. Evidently, MMPs are widely circulated in the brain and regulate various process including microglial activation, inflammation, blood-brain barrier disruption as well as affects central nervous system (CNS). The present study was to assess the association of single nucleotide polymorphisms of MMP-2, MMP-9 and chemokine (CXCL-12/SDF1-3’) in the north Indian population. Methods: We performed case-control study comprising of 125 patients and 125 healthy controls in north Indian population. Genomic DNA was extracted from whole blood and gene polymorphism have been determined by PCR-RFLP method. Results: MMP-2, MMP-9 and CXCL-12 gene was not significantly associated with JE disease, but homozygous (T/T) genotype of MMP-2 was statically associated with disease outcome (p=0.05, OR=0.110). A/G and G/G genotype of CXCL-12 was significantly associated with severity of disease. (p=0.032, OR=5.500, p=0.037, OR= 9.167). The serum level of MMP-2 was observed significantly increased in JE patients with homozygous (T/T) genotype whereas increased MMP-9 level was associated with heterozygous genotype. Interpretation & conclusion: MMP-2, MMP-9 and CXCL-12 gene polymorphism were not associated with JE susceptibility, but MMP-2 may be contributed to disease protection. CXCL-12 was associated with disease severity. In our concern this is the first report from northern India.

MiR-30e-5p overexpression promotes proliferation and migration of colorectal cancer cells by activating the CXCL12 axis via downregulating PTEN / 南方医科大学学报

OBJECTIVE@#To investigate the regulatory effects of miR-30e-5p on biological behaviors of colorectal cancer cells and the role of PTEN/CXCL12 axis in mediating these effects.@*METHODS@#Bioinformatic analysis was performed to explore the differential expression of miR-30e-5p between colorectal cancer tissues and normal tissues. RT-qPCR was used to detect the differential expression of miR-30e-5p in intestinal epithelial cells and colorectal cancer cells. Bioinformatics and dual luciferase assay were used to predict and validate the targeting relationship between miR-30e-5p and PTEN. Human and murine colorectal cancer cell lines were transfected with miR-30e-5p mimics, miR-30e-5p inhibitor, miR-30e-5p mimics+LV-PTEN, or miR-30e-5p inhibitor + si-PTEN. The changes in biological behaviors of the cells were detected using plate clone formation assay, CCK-8 assay, flow cytometry, scratch healing and Transwell assays. PTEN and CXCL12 expressions in the cancer cells were detected by Western blotting. The effects of miR-30e-5p inhibitor on colorectal carcinogenesis and development were observed in nude mice.@*RESULTS@#Bioinformatic analysis showed that miR-30e-5p expression was significantly elevated in colorectal cancer tissues compared with the adjacent tissue (P < 0.01). Higher miR-30e-5p expression was detected in colorectal cancer cell lines than in intestinal epithelial cells (P < 0.01). Dual luciferase assay confirmed the targeting relationship between miR-30e-5p and PTEN (P < 0.05). Transfection with miR-30e-5p mimics significantly enhanced proliferation and metastasis and inhibited apoptosis of the colorectal cancer cells (P < 0.05), and co-transfection with LV-PTEN obviously reversed these changes (P < 0.05). MiR-30e-5p mimics significantly inhibited PTEN expression and enhanced CXCL12 expression in the cancer cells (P < 0.01), and miR-30e-5p inhibitor produced the opposite effect. Transfection with miR-30e-5p inhibitor caused cell cycle arrest in the cancer cells, which was reversed by co-transfection with si-PTEN (P < 0.05). In the in vivo experiments, the colorectal cancer cells transfected with miR-30e-5p inhibitor showed significantly lowered tumorigenesis.@*CONCLUSION@#Overexpression of miR-30e-5p promotes the malignant behaviors of colorectal cancer cells by downregulating PTEN to activate the CXCL12 axis.

Advances in the study on cytokines related to dental pulp regeneration / 口腔医学

@#With the development of molecular biology, biomaterials and tissue engineering, regenerative treatment of pulpal and periradicular diseases is facing new opportunities. At present, a large number of studies on dental pulp regeneration reveal that cytokines are essential for promoting migration, proliferation and osteogenic differentiation of dental pulp stem cells. In this paper, we review several kinds of cytokines related to dental pulp regeneration, and analyze their roles and regulatory mechanisms in dental pulp regeneration.

Carnosic acid affects the proliferation, migration, and invasion of gastric cancer AGS cells by regulating CXCR7/CXCL12 axis / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨鼠尾草酸（CA）通过调节CXC基序趋化因子受体7（CXCR7）/CXC基序趋化因子配体（CXCL12）轴对胃癌AGS细胞增殖、迁移和侵袭的影响。方法：用不同浓度（0、5、10、20、40、80 µg/mL））的CA处理胃癌AGS细胞，采用CCK-8法筛选合适的CA浓度；将AGS细胞分为对照组（未经处理的AGS细胞）、CA组（20 µg/mL CA处理）、CA+siCXCR7组（转染siCXCR7+20 µg/mL CA处理）、CA+siNC组（转染siNC+20 µg/mL CA处理）、CA+vectorNC组（转染vectorNC+20 µg/mL CA处理）、CA+vectorCXCR7组（转染vectorCXCR7+20 µg/mL CA处理），采用CCK-8法检测AGS细胞增殖的变化，qPCR法检测细胞中CXCR7、CXCL12 mRNA表达水平的变化，Transwell实验检测细胞侵袭能力的变化，划痕实验检测细胞迁移能力的变化，WB法检测周期蛋白D1、Bcl-2、CXCR7、CXCL12、MMP-2蛋白表达的变化。结果：不同浓度CA均可抑制AGS细胞存活率，且浓度为20 µg/mL时，细胞存活率接近50%，故选择20 µg/mL CA用于后续研究。与对照组相比，CA组增殖率、侵袭数、迁移率、周期蛋白D1、MMP-2、Bcl-2、CXCR7、CXCL12 mRNA及蛋白表达显著降低（均P<0.05）；与CA+siNC组相比，CA+siCXCR7组增殖率、侵袭数、迁移率、周期蛋白D1、MMP-2、Bcl-2、CXCR7、CXCL12 mRNA及蛋白表达显著降低（均P<0.05）；与CA+vectorNC组相比，CA+vectorCXCR7组增殖率、侵袭数、迁移率、周期蛋白D1、MMP-2、Bcl-2、CXCR7、CXCL12 mRNA及蛋白表达显著增加（均P<0.05）。结论：CA可抑制AGS细胞增殖、迁移和侵袭，其机制可能与抑制CXCR7/CXCL12轴有关。

Yigong Powder regulates CXCL12/CXCR4 signaling to reduce glutamate release and prevent cognitive decline in mouse model of aging / 中国中药杂志

This study aims to explore the effect of preventive administration of Yigong Powder on the learning and memory abilities of the mouse model of aging induced by D-galactose and decipher the underlying mechanism, so as to provide a basis for the application of Yigong Powder in the prevention and treatment of cognitive decline. Forty KM mice were randomized into control, model, donepezil(1.5 mg·kg~(-1)), and high-dose(7.5 g·kg~(-1)) and low-dose(3.75 g·kg~(-1)) Yigong Powder groups. The mice in other groups except the control group were injected with D-galactose(200 g·kg~(-1)) at the back of the neck for the modeling of aging. At the same time, the mice were administrated with corresponding drugs by gavage for one month. Morris water maze was used to examine the learning and memory abilities of the mice. Hematoxylin-eosin staining was employed to observe the pathological and morphological changes of the hippocampus. The immunofluorescence assay was employed to detect the expression of ionized calcium-binding adapter molecule 1(IBA1), glial fibrillary acidic protein(GFAP), chemokine C-X-C-motif ligand 12(CXCL12), chemokine C-X-C-motif receptor 4(CXCR4) in the hippocampus and observe the positional relationship between IBA1, GFAP, and CXCR4. Western blot was employed to determine the protein levels of extracellular regulated kinase(ERK), p-ERK, and tumor necrosis factor receptor 1(TNFR1). Enzyme-linked immunosorbent assay was employed to measure the levels of glutamate and tumor necrosis factor(TNF-α) in the brain tissue and the level of TNF-α in the serum and spleen. Yigong Powder significantly shortened the escape latency, increased the times crossing platforms, and prolonged the cumulative time in quadrants of the aging mice. It alleviated the nerve cell disarrangement, increased intercellular space, and cell degeneration or death in the hippocampus and reduced the pathology score of the damaged nerve. Moreover, Yigong Powder reduced the positive area of IBA1 and GFAP, reduced the levels of TNF-α in the brain tissue, serum, and spleen, and decreased spleen index. Furthermore, Yigong Powder decreased the average fluorescence intensity of CXCL12 and CXCR4, reduced CXCR4-positive astrocytes and microglia, down-regulated the protein levels of p-ERK/ERK and TNFR1, and lowered the level of glutamate in the brain tissue. This study showed that the preventive administration of Yigong Powder can ameliorate the learning and memory decline of the D-galactose-induced aging mice by regulating the immune function of the spleen and the CXCL12/CXCR4 signaling in the brain to reduce glutamate release. However, the mechanism of Yigong San in preventing and treating dementia via regulating spleen and stomach function remains to be studied.

Reversing the PAI-1-induced fibrotic immune exclusion of solid tumor by multivalent CXCR4 antagonistic nano-permeator

Fibrosis is one of the key factors that lead to the immune exclusion of solid tumors. Although degradation of fiber is a promising strategy, its application was still bottlenecked by the side effects of causing metastasis, resulting in the failure of immunotherapy. Here, we developed an antimetastatic polymer (HPA) for the delivery of chemo-drug and antifibrotic siPAI-1 to form the nano-permeator. Nano-permeator shrank after protonation and deeply penetrated into the tumor core to down-regulate the expression of PAI-1 for antifibrosis, and further promoted the sustained infiltration and activation of T cells for killing tumor cells. Moreover, metastasis after fiber elimination was prevented by multivalent CXCR4 antagonistic HPA to reduce the attraction of CXCL12 secreted by distant organs. The administration of stroma-alleviated immunotherapy increased the infiltration of CD8+ T cells to 52.5% in tumor tissues, inhibiting nearly 90% metastasis by HPA in distant organs. The nano-permeator reveals the mechanism and correlation between antifibrosis and antimetastasis and was believed to be the optimizing immunotherapy for solid fibrotic tumors.

Research progress of C-X-C motif chemokine ligand 12 and its receptor signaling axis in the regulation of pulmonary fibrosis / 中华劳动卫生职业病杂志

Pulmonary fibrosis is an irreversible interstitial lung disease characterized by lung parenchyma remodeling and collagen deposition. In recent years, the incidence and mortality of pulmonary fibrosis caused by unknown causes have risen. However, its pathogenesis is still unclear. C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C chemokine receptor 4 (CXCR4)/CXCR7 signal axis plays a critical regulatory role in pulmonary fibrosis disease. In addition, the signal axis has been shown to regulate recruitment and migration of circulating fibrocytes, mesenchymal stem cells to the damage lung tissue, the migration of endothelial cells, the proliferation and differentiation of fibroblasts and endothelial cells, which further affects the occurrence and progression of pulmonary fibrosis. In this review, we summarized the pathogenesis and treatment research progress of CXCL12 and its receptor CXCR4/CXCR7 in the occurrence and progression of pulmonary fibrosis.

Serum CXCL12 predicts the outcomes after intravenous thrombolytic therapy in patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the correlation between serum CXCL12 and the outcomes after intravenous thrombolytic therapy in patients with acute ischemic stroke.Methods:Consecutve patients with acute ischemic stroke treated with intravenous thrombolytic therapy in the Department of Neurology, the First Affiliated Hospital of Soochow University from January 1, 2020 to August 31, 2021 were enrolled retrospectively. Serum CXCL12 was measured by enzyme-linked immunosorbent assay within 24 h of onset. No improvement in early neurological function was defined as the National Institutes of Health Stroke Scale (NIHSS) 24 h after thrombolysis decreased by <4 compared with the baseline. The clinical outcome was evaluated by the modified Rankin Scale at 90 d after onset, and >2 were defined as a poor outcome. Multivariate logistic regression analysis was used to evaluate the correlation between serum CXCL12 and the outcome after intravenous thrombolysis, and the predictive value of serum CXCL12 for no improvement of early neurological function and poor short-term outcome was analyzed by the receiver operating characteristic (ROC) curve. Results:A total of 66 patients were enrolled, and the serum CXCL12 was 15.72±6.52 g/L. Twenty-seven patients (40.9%) had poor outcomes, and 34 (51.5%) had no improvement in early neurological function. Multivariate logistic regression analysis showed that higher serum CXCL12 was an independent predictor of poor outcome (odds ratio [ OR] 1.245, 95% confidence interval [ CI] 1.093-1.419; P=0.001) and no improvement in early neurological function ( OR 1.250, 95% CI 1.100-1.420; P=0.001). ROC curve analysis showed that the area under the curve of serum CXCL12 for predicting poor outcome was 0.793 (95% CI 0.679-0.908), the best cut-off value was 15.38 μg/L, and the corresponding sensitivity and specificity were 81.5% and 76.9%, respectively. The area under the curve of serum CXCL12 for predicting no improvement of early neurological function was 0.849 (95% CI 0.748-0.951), and the best cut-off value was 15.68 μg/L, and the corresponding sensitivity and specificity were 76.5% and 87.5%, respectively. Conclusion:Serum CXCL12 had a better predictive value for the outcomes of patients with acute ischemic stroke after intravenous thrombolytic therapy.

Biological Functions of CXCL12-CXCR4 in Human Malignant Tumors / 中国生物化学与分子生物学报

Metastasis and cell infiltration are the difficulties in the treatment of solid and lymphatic carcinoma and the main causes of disease recurrence and death. The migration of cancer cells is a prerequisite for tumor metastasis and invasion. The CXCL12-CXCR4 pathway plays an important role in the pathogenesis of solid tumors and leukemia. The interaction between CXCL12 and its receptor CXCR4 can activate multiple signaling pathways and regulate different physiological and pathophysiological processes. Thus, blocking CXCL12-CXCR4 binding and / or downstream pathways has clinical benefits in treating a variety of diseases and cancers. Although some CXCL12 and CXCR4 antagonists have been identified and have shown encouraging results in terms of antitumor activity, these drugs have not been widely used in clinical patients due to their serious toxic and side effects. There is an urgent need to develop novel CXCL12-CXCR4 axis antagonists for the treatment of tumors. Herein, we review the recent research progress of CXCR4 pathway in solid tumors and leukemia, and discuss the therapeutic value and future research direction of CXCR4 pathways in solid tumors and leukemia.

AHVAC-I reverses tumor growth of cancer-associated fibroblasats in gastric cancer / 中国临床药理学与治疗学

AIM: To explore whether Agkistrodon Halys venom antitumor component-I (AHVAC-I) affects the migration of gastric cancer cells by human primary gastric cancer-associated fibroblast (GCAFs). METHODS: Tissue block culture and trypsin digestion were used to separate and culture human primary gastric cancer-associated fibroblasts (GCAFs); the GCAFs-CM

Effect of chronic emotional stress induced by empty bottle stimulation on inflammatory factors in rats with acute myocardial infarction: analysis of the CXCL12/CXCR4 axis / 南方医科大学学报

OBJECTIVE@#To investigate the effect of chronic emotional stimulation induced by empty bottle stimulation on CXCL12/CXCR4-mediated inflammatory response in rats with acute myocardial infarction (AMI).@*METHODS@#Rat models of anxiety were established by a 21-day stimulation with uncertain empty bottle drinking water, and myocardial infarction was induced by ligating the left anterior descending branch of the coronary artery; compound models were established by performing myocardial infarction operation on the 15th day of anxiety modeling. The rats were randomly divided into 4 groups: shamoperated group (=6), myocardial infarction group (=6), compound model group (with myocardial infarcted and anxiety; = 6), and inhibitor group (compound models treated daily with 1 mg/kg AMD3100 for 6 days; =7). Echocardiography was used to examine the LVEF and LVFS to evaluate the cardiac function of the rats. Elevated maze test and open field test were used to evaluate the behaviors of the rats. The expressions of CXCL12, CXCR4, IL-1β, IL-18 and neutrophil active protease (NE) in the myocardial tissues and blood samples were detected with ELISA and immunohistochemistry.@*RESULTS@#The LVEF and LVFS were lower in the compound model group than in the sham group and myocardial infarction group ( < 0.05), and were higher in inhibitor group than in the compound model group ( < 0.05). LVID; d and LVID; s were lower in the inhibitor group than in the compound model group ( < 0.05). Compared to those in the sham group and myocardial infarction group, the rats in the compound model group more obviously preferred to stay in the closed arm ( < 0.05) in EPM; the rats in the inhibitor group had more times of entering and staying in the open arm than the compound model rats ( < 0.05); the horizontal and vertical movements were less in the compound model rats than in those in the sham group and the myocardial infarction group ( < 0.05) in OFT, and the vertical movement of the rats in inhibitor group was higher than those in the compound model group ( < 0.05). The expression of CXCR4 in the marginal zone of myocardial infarction was significantly higher in the compound model group than in the sham-operated group, myocardial infarction group and inhibitor group ( < 0.05). The expressions of IL-1β, IL-18 and NE in the inhibitor group were significantly lower than those in the compound model group ( < 0.05). Compared with at in the sham-operated group, the number of Nissl bodies in the compound model group decreased significantly ( < 0.01).@*CONCLUSIONS@#Chronic emotional stress induced by empty bottle stimulation can lead to dysfunction of the CXCL12/CXCR4 axis, which causes inflammatory cascade after myocardial infarction to worsen myocardial cell necrosis, cardiac function and hippocampal neuronal damage after the infarction.

IL-17A activates mouse lung fibroblasts through promoting chemokine CXCL12 secretion / 浙江大学学报·医学版

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.

Expression and clinical significance of SDF-1 and CXCR4 in peripheral blood of patients with hepatitis C cirrhosis / 中国医师杂志

Objective To detect the expression and clinical significance of stro-mal cell derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) in peripheral blood of patients with hepatitis C cirrhosis.Methods From January 2015 to January 2018,120 patients with hepatitis C cirrhosis in our hospital were selected as the subjects,including 60 patients with compensated hepatitis C cirrhosis and 60 patients with decompensated hepatitis C cirrhosis,and 60 hepatitis C patients without cirrhosis in the same period were selected as the control group.Enzyme linked immunosorbent assay (ELISA) was used to detect the expression levels of SDF-1 and CXCR4 in peripheral blood;the correlation between SDF-1 and CXCR4 expressions in compensated cirrhosis and decompensated cirrhosis patients was analyzed.Results The expression levels of SDF-1 and CXCR4 in peripheral blood samples of patients with decompensated cirrhosis of hepatitis C were significantly higher than those of patients with compensated cirrhosis of hepatitis C (P ＜ 0.05);the expression levels of SDF-1 and CXCR4 in peripheral blood samples of patients with compensated and decompensated cirrhosis of hepatitis C were significantly higher than those of control group (P ＜ 0.05);the expressions of SDF-1 and CXCR4 in peripheral blood of patients with compensated and decompensated cirrhosis of hepatitis C were positively correlated (r =0.684,P ＜ 0.05,r =0.765,P ＜ 0.05).Albumin (AlB) level in peripheral blood of cirrhosis group was significantly lower than that of control group (P ＜ 0.05);alanine aminotransferase (ALT),aspartate aminotransferase (AST),total bilirubin (TBIL),while fasting insulin (FINs) and interleukin (IL)-6 in cirrhosis group were higher than those of control group (P ＜ 0.05);SDF-1 level and CXCR4 level were positively correlated with AlB,FINs and IL-6 (P ＜ 0.05);multiple regression analysis showed that FINs,IL-6,SDF-1 and CXCR4 were risk factors for hepatitis C cirrhosis.Conclusions The levels of SDF-1 and CXCR4 in peripheral blood of patients with hepatitis C cirrhosis increased,and the levels of SDF-1 and CXCR4 in peripheral blood were positively correlated,suggesting that they may be involved in the regulation of the occurrence and development of hepatitis C cirrhosis.

A CXCL12/CXCR4 axis in regulation of tumor behaviors by ionizing radiation / 中华放射医学与防护杂志

In addition to induce cell death in tumor cells, ionizing radiation (IR) regulates many biological behaviors of malignant tumors, such as intrinsic radiosensitivity, invasion and metastasis, angiogenesis, as well as immune response of tumor cells. The C-X-C motif chemokine ligand 12 (CXCL12) and its receptor CXCR4 are highly expressed in a variety of malignant tumors, and are involved in the process of remote metastasis, blood vessel formation, immune regulation, and therapeutic resistance of malignant tumors. Recent studies have found that the CXCL12/CXCR4 signal axis plays critical roles in the IR-regulated biological behavior of malignant tumors. This paper reviews the roles of CXCL12/CXCR4 signal axis in the biological behavior changes of irradiated malignant tumors.

Chemokine receptor CXCR7 assists CXCR4 in modulating the directional metastasis and EMT of pancreatic cancer / 西安交通大学学报(医学版)

Objective: To investigate the effect of CXCL12/CXCR4/CXCR7 axis on the metastasis and invasion in pancreatic cancer so as to provide new evidence for research on pancreatic cancer metastasis treatment. Methods: MiaPaCa-2 cells were transfected with CXCR4 shRNA and CXCR7 shRNA, and the Transwell assay was used to determine the effects of CXCL12/CXCR4/CXCR7 axis on cell invasion and migration. Quantitative RT-PCR and Western blotting were used to explore the effects of CXCL12/CXCR4/CXCR7 axis on the expressions of invasion-related genes (MMP-2 and uPA) and EMT-related genes (E-cadherin and Vimentin). Results: CXCL12 significantly increased the metastasis and invasion of pancreatic cancer cells. The enhancement of tumor cell invasion was effectively countered by CXCR4 shRNA or CXCR7 shRNA. CXCL12/CXCR4 axis in cancer cells increased the expressions of invasion-related genes (MMP-2 and uPA) and EMT-related genes (E-cadherin and Vimentin). CXCL12/CXCR7 axis only increased the expressions of MMP-2 and uPA. Compared to blocking CXCR4 or CXCR7 alone, the inhibitory effects on invasion-related genes and EMT-related genes were more effective when both CXCR4 and CXCR7 were blocked. Conclusion: CXCL12/CXCR4/CXCR7 axis regulates the EMT, metastasis, and invasion of pancreatic cancer cells.

A CXCL12/CXCR4 axis in regulation of tumor behaviors by ionizing radiation / 中华放射医学与防护杂志

In addition to induce cell death in tumor cells,ionizing radiation (IR) regulates many biological behaviors of malignant tumors,such as intrinsic radiosensitivity,invasion and metastasis,angiogenesis,as well as immune response of tumor cells.The C-X-C motif chemokine ligand 12 (CXCL12) and its receptor CXCR4 are highly expressed in a variety of malignant tumors,and are involved in the process of remote metastasis,blood vessel formation,immune regulation,and therapeutic resistance of malignant tumors.Recent studies have found that the CXCL12/CXCR4 signal axis plays critical roles in the IR-regulated biological behavior of malignant tumors.This paper reviews the roles of CXCL12/CXCR4 signal axis in the biological behavior changes of irradiated malignant tumors.

Biological characteristics of stromal cell-derived factor-1/CXC chemokine receptor 4 signal axis / 中国组织工程研究

BACKGROUND: Nowadays, stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) signal axis has been used extensively because of its biological effects and particularly a great progress has been achieved in the mechanism of SDF-1/CXCR4 signal axis as well as in its use for tissue regeneration. OBJECTIVE: To summarize the factors affecting the regulation of SDF-1 and CXCR4 and to review the research progress in the biological characteristics of SDF-1/CXCR4 signal axis. METHODS: The first author searched the PubMed, CNKI, WanFang and VIP databases for relevant articles published from January 1990 to August 2018. The keywords were "tissue engineering; cell homing; chemokine; regeneration; pulp regeneration; HIF-1; SDF-1; CXCL12; CXCR4; NOX-A12" in both Chinese and English. RESULTS AND CONCLUSION: Hypoxia-inducible factor-1 plays a key role in the regulation of SDF-1, and there are multiple factors which can affect the expression of CXCR4. SDF-1/CXCR4 signal axis formed by the combination of SDF-1 and CXCR4 plays an important biological role in various physiological and pathological processes. Blocking SDF-1 is used to inhibit the pathogenic effect of the SDF-1/CXCR4 signal axis for therapeutic purposes, while increasing SDF-1 can strengthen the SDF-1/CXCR4 signal axis and enhance the ability of chemotactic endogenous cell homing for tissue regeneration. To further illustrate the mechanism of the SDF-1/CXCR4 signal axis, we upregulate or downregulate the expression of SDF-1 or CXCR4 by exogenous means to influence the biological function of the signal axis, and thus provide theoretical basis for optimizing clinical treatment strategies, and developing the biological function of the signal axis for human health benefits.

Research progress of chemokines and their receptors in hepatocellular carcinoma / 国际外科学杂志

Chemokines and their receptors play an important role in the occurance and development of hepatocellular carcinoma(HCC).The effects of chemokines and their receptors in HCC are different,chemokines and their receptors associated with HCC are mostly expressed in promoting tumor cell proliferation,angiogenesis and invasion,but some chemokines and their receptors play an anti-tumor role.This reviews focus on the role of chemokines and their receptors in HCC.

Expression and significance of CXCL12, CXCR4, MVD in MM bone marrow micro niche / 重庆医学

Objective To study expression,distribution,significance and relationship of CXCL12,CXCR4,microvessel density (MVD) in multiple myeloma (MM) bone marrow micro niche.Methods 63 cases of patients with MM were chosen as the experimental group,42 cases of healthy persons were chosen as the control group.The expression and distribution of CXCL12,CXCR4,MVD were detected by immunohistochemical method.Results Compared with the control group,the expressions of CXCL12,CXCR4,MVD in the experimental group were higher,the difference was statistically significant (P ＜ 0.05),their expressions in bone marrow were not significantly different from gender,age,immunoglobulin type and light chain classification (P＞0.05);the expression of CXCR4,MVD were positively related with CXCL12 (P＜0.05).Conclusion The expression of CXCL12,CXCR4,MVD may be related to the occurrence of MM;CXCL12/CXCR4 biological axis could promote the angiogenesis of MM bone marrow micro niche.