C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.

CC-chemokine receptor 7 and its ligand CCL 19 promote mitral valve interstitial cell migration and repair

The effect of CC-chemokine receptor 7 （CCR7） and CC-chemokine ligand 19 （CCL19） on rheumatic mitral ste- nosis is unknown. This study aimed to explore the roles of CCR7 and CCL19 in rheumatic mitral stenosis by mea- suring the expression of CCR7 and CCL19 in human mitral valves from rheumatic mitral stenosis patients. Additionally, we examined their effects on human mitral valve interstitial cells （hMVICs） proliferation, apoptosis and wound repair. CCR7 and CCL19 expression was measured in the mitral valves from rheumatic mitral stenosis patients （n= 10） and compared to normal mitral valves （n=5）. CCR7 was measured in cultured hMVICs from rheu- matic mitral stenosis patients and normal donors by RT-PCR and immunofluorescence. The cells were also treated with exogenous CCL19, and the effects on wound healing, proliferation and apoptosis were assayed. In the rheu- matic mitral valves, valve interstitial cells expressed CCR7, while mononuclear cells and the endothelium expressed CCL19. Healthy mitral valves did not stain positive for CCR7 or CCL19. CCR7 was also detected in cultured rheu- matic hMVICs or in normal hMVICs treated with CCL19. In a wound healing experiment, wound closure rates of both rheumatic and normal hMVICs were significantly accelerated by CCL19. These effects were abrogated by a CCR7 neutralizing antibody. The CCR7/CCL19 axis did not influence the proliferation or apoptosis of hMVICs, indicating that wound healing was due to increased migration rates rather than increased proliferation. In conclu- sion, CCR7 and CCL19 were expressed in rheumatic mitral valves. The CCR7/CCL19 axis may regulate remodel- ing of rheumatic valve injury through promoting migratory ability of hMVICs.

C-C chemokine receptor type 2-overexpressing exosomes alleviated experimental post-stroke cognitive impairment by enhancing microglia/macrophage M2 polarization

BACKGROUND Human-derived mesenchymal stromal cells have been shown to improve cognitive function following experimental stroke.The activity of exosomes has been verified to be comparable to the therapeutic effects of mesenchymal stromal cells.However,the effects of exosomes derived from human umbilical cord mesenchymal stem cells(HUC-MSCs)(ExoCtrl)on post-stroke cognitive impairment(PSCI)have rarely been reported.Moreover,whether exosomes derived from C-C chemokine receptor type 2(CCR2)-overexpressing HUC-MSCs(ExoCCR2)can enhance the therapeutic effects on PSCI and the possible underlying mechanisms have not been studied.AIM To investigate the effects of ExoCtrl on PSCI and whether ExoCCR2 can enhance therapeutic effects on PSCI.METHODS Transmission electron microscopy,qNano®particles analyzer,and Western blotting were employed to determine the morphology and CCR2 expression of ExoCtrl or ExoCCR2.ELISA was used to study the binding capacity of exosomes to CC chemokine ligand 2(CCL2)in vivo.After the intravenous injection of ExoCtrl or ExoCCR2 into experimental rats,the effect of ExoCtrl and ExoCCR2 on PSCI was assessed by Morris water maze.Remyelination and oligodendrogenesis were analyzed by Western blotting and immunofluorescence microscopy.QRT-PCR and immunofluorescence microscopy were conducted to compare the microglia/macrophage polarization.The infiltration and activation of hematogenous macrophages were analyzed by Western blotting and transwell migration analysis.RESULTS CCR2-overexpressing HUC-MSCs loaded the CCR2 receptor into their exosomes.The morphology and diameter distribution between ExoCtrl and ExoCCR2 showed no significant difference.ExoCCR2 bound significantly to CCL2 but ExoCtrl showed little CCL2 binding.Although both ExoCCR2 and ExoCtrl showed beneficial effects on PSCI,oligodendrogenesis,remyelination,and microglia/macrophage polarization,ExoCCR2 exhibited a significantly superior beneficial effect.We also found that ExoCCR2 could suppress the CCL2-induced macrophage migration and activation in vivo and in vitro,compared with ExoCtrl treated group.CONCLUSION CCR2 over-expression enhanced the therapeutic effects of exosomes on the experimental PSCI by promoting M2 microglia/macrophage polarization,enhancing oligodendrogenesis and remyelination.These therapeutic effects are likely through suppressing the CCL2-induced hematogenous macrophage migration and activation.Key words:Cognitive impairment;Stroke;Exosomes;C-C chemokine receptor type 2;Microglia/macrophage polarization;Remyelination.

C-X-C chemokine receptor type 7 antibody enhances neural plasticity after ischemic stroke

Stromal cell-derived factor-1 and its receptor C-X-C chemokine receptor 4(CXCR4) have been shown to regulate neural regeneration after stroke.Howeve r,whether stromal cell-derived factor-1 receptor CXCR7,which is widely distributed in the develo ping and adult central nervous system,participates in neural regeneration remains poorly unde rstood.In this study,we established rat models of focal cerebral ischemia by injecting endothelin-1 into the cerebral co rtex and striatum.Starting on day 7 after injury,CXCR7-neutralizing antibody was injected into the lateral ventricle using a micro drug delivery system for 6 consecutive days.Our results showed that CXCR7-neutralizing antibody increased the total length and number of sprouting co rticospinal tra ct fibers in rats with cerebral ischemia,increased the expression of vesicular glutamate transporter 1 and growth-related protein 43,marke rs of the denervated spinal cord synapses,and promoted the differentiation and maturation of oligodendrocyte progenitor cells in the striatum.In addition,CXCR7 antibody increased the expression of CXCR4 in the striatum,increased the protein expression of RAS and ERK1/2 associated with the RAS/ERK signaling pathway,and im proved rat motor function.These findings suggest that CXCR7 improved neural functional recovery after ischemic stroke by promoting axonal regeneration,synaptogenesis,and myelin regeneration,which may be achieved by activation of CXCR4 and the RAS/ERK1/2 signaling pathway.

CXCL12 Retargeting of an Oncolytic Adenovirus Vector to the Chemokine CXCR4 and CXCR7 Receptors in Breast Cancer

Breast cancer is the most frequently diagnosed cancer in women under 60, and the second most diagnosed cancer in women over 60. While significant progress has been made in developing targeted therapies for breast cancer, advanced breast cancer continues to have high mortality, with poor 5-year survival rates. Thus, current therapies are insufficient in treating advanced stages of breast cancer;new treatments are sorely needed to address the complexity of advanced-stage breast cancer. Oncolytic virotherapy has been explored as a therapeutic approach capable of systemic administration, targeting cancer cells, and sparing normal tissue. In particular, oncolytic adenoviruses have been exploited as viral vectors due to their ease of manipulation, production, and demonstrated clinical safety profile. In this study, we engineered an oncolytic adenovirus to target the chemokine receptors CXCR4 and CXCR7. The overexpression of CXCR4 and CXCR7 is implicated in the initiation, survival, progress, and metastasis of breast cancer. Both receptors bind to the ligand, CXCL12 (SDF-1), which has been identified to play a crucial role in the metastasis of breast cancer cells. This study incorporated a T4 fibritin protein fused to CXCL12 into the tail domain of an adenovirus fiber to retarget the vector to the CXCR4 and CXCR7 chemokine receptors. We showed that the modified virus targets and infects CXCR4- and CXCR7-overexpressing breast cancer cells more efficiently than a wild-type control vector. In addition, the substitution of the wild-type fiber and knob with the modified chimeric fiber did not interfere with oncolytic capability. Overall, the results of this study demonstrate the feasibility of retargeting adenovirus vectors to chemokine receptor-positive tumors.

Functions and mechanisms of chemokine receptor 7 in tumors of the digestive system

Chemokine(C-X-C motif)receptor 7(CXCR7),recently termed ACKR3,belongs to the G protein-coupled cell surface receptor family,binds to stromal cellderived factor-1[SDF-1,or chemokine(C-X-C motif)ligand 12]or chemokine(CX-C motif)ligand 11,and is the most common chemokine receptor expressed in a variety of cancer cells.SDF-1 binds to its receptor chemokine(C-X-C motif)receptor 4(CXCR4)and regulates cell proliferation,survival,angiogenesis and migration.In recent years,another new receptor for SDF-1,CXCR7,has been discovered,and CXCR7 has also been found to be expressed in a variety of tumor cells and tumor-related vascular endothelial cells.Many studies have shown that CXCR7 can promote the growth and metastasis of a variety of malignant tumor cells.Unlike CXCR4,CXCR7 exhibits a slight modification in the DRYLAIV motif and does not induce intracellular Ca^2+release following ligand binding,which is essential for recruiting and activating G proteins.CXCR7 is generally thought to work in three ways:(1)Recruitingβ-arrestin 2;(2)Heterodimerizing with CXCR4;and(3)Acting as a“scavenger”of SDF-1,thus lowering the level of SDF-1 to weaken the activity of CXCR4.In the present review,the expression and role of CXCR7,as well as its prognosis in cancers of the digestive system,were investigated.

The value and association of CC chemokine receptor 7 expression in non-small cell lung cancer with lymph nodes metastasis

Objective： The aim of this study was to analyze the expression of CC chemokine receptor 7 （CCR7） in pulmonary tumor tissue and metastasized lymph nodes of non-small cell lung cancer （NSCLC）, explore the relationship between the expressions of CCR7 in pulmonary tumor tissue and metastasized lymph nodes, and discuss the significance. Methods： SABC immunohistochemical staining was used to investigate the expression of CCR7 by rabbit anti-human CCR7 monoclonal antibody, and the specimens were 17 cases of adenocarcinoma, 17 cases of squamous cell carcinoma, 12 cases of adenosquamous carcinoma, 4 cases of large cell carcinoma and 28 cases of metastasized lymph nodes of lung cancer. Negative control sections used 5 cases of inflammatory pseudotumor and 20 cases of normal lung tissue. Two independent pathologists observed all the specimens in the high power field （x 400） of microscope by double blind method. Results： （1） The expression of CCR7 in pulmonary tumor tissue was stronger than normal lung tissue （P 〈 0.005）; （2） The expressions of CCR7 in pulmonary tumor tissues and metastasized lymph nodes had no significant differences （P = 0.177）; （3） The expression of CCR7 had correlation with lymph nodes metastasis, and the expression in lymph nodes metastasis group was more than that of no lymph nodes metastasis group （P = 0.016）; （4） Along with the increment of clinical stage, the CCR7 expression had a tendency to increase （P = 0.003）. Conclusion： CCR7 has rich expression in carcinoma cell nests and lymph node metastasis. It demonstrates that CCR7 may be related to the development of lymph node metastasis in NSCLC.

原发性肝癌组织CCR7、MCM10蛋白与临床病理特征及预后的相关性

目的 探讨原发性肝癌(PHC)组织趋化因子受体7(CCR7)、微染色体维持蛋白10(MCM10)与临床病理特征及预后的相关性。方法 选取2017年1月至2020年12月周口市中心医院90例PHC患者为研究对象,均行肝癌切除术,术中取肿瘤组织及癌旁正常组织。比较PHC不同组织CCR7、MCM10蛋白表达,χ^(2)检验分析CCR7、MCM10表达与临床病理特征的关系,Kaplan-Meier分析CCR7、MCM10蛋白表达与PHC患者预后的关系,Cox回归分析PHC患者预后影响因素,Kaplan-Meier分析CCR7、MCM10蛋白表达亚组与PHC患者预后的关系。结果 PHC患者肿瘤组织中CCR7、MCM10蛋白阳性表达分别为66.67%、75.56%,高于正常组织的23.33%、27.78%,差异有统计学意义(P<0.05);有淋巴结转移、血管侵犯患者癌组织中CCR7、MCM10蛋白阳性表达率(79.25%、94.34%,81.58%、89.47%)高于无淋巴结转移、血管侵犯患者(48.65%、48.65%,55.77%、65.38%),差异有统计学意义(P<0.05);Kaplan-Meier生存分析显示,CCR7、MCM10蛋白阳性表达患者的3 a生存率分别为39.66%(23/58)、41.54%(27/65),低于阴性表达患者的68.97%(20/29)、72.73%(16/22),差异有统计学意义(P<0.05);Cox回归分析显示,淋巴结转移(95%CI:1.129~3.025)、血管侵犯(95%CI:1.463~3.147)、CCR7蛋白(95%CI:1.407~3.524)、MCM10蛋白(95%CI:1.384~3.441)均为PHC患者预后的独立危险因素(P<0.05);Kaplan-Meier分析显示,CCR7蛋白阳性+MCM10蛋白阳性亚组预后最差,CCR7蛋白阴性+MCM10蛋白阴性亚组预后最好,各亚组间比较差异均有统计学意义(P<0.05)。结论 PHC组织CCR7、MCM10蛋白表达与临床病理特征及预后相关,二者均阳性表达是预后不良的危险因素,可作为临床评估病情、预测预后的辅助指标,并对临床防治具有一定指导意义。

血清CXCR7、SGK1水平与急性心肌梗死经皮冠状动脉介入治疗术后预后不良的关系

目的探讨血清C-X-C基序趋化因子受体7(CXCR7)、血清/糖皮质激素调节激酶1(SGK1)水平与急性心肌梗死(AMI)经皮冠状动脉介入治疗(PCI)术后预后不良的关系。方法选取2020年9月—2022年12月于南京医科大学第二附属医院急诊科接受PCI术的AMI患者100例为AMI组,同期医院健康体检者50例为健康对照组,根据PCI术后1年预后情况将AMI患者分为预后不良亚组30例和预后良好亚组70例。采用酶联免疫吸附法检测血清CXCR7、SGK1水平;多因素Logistic回归分析AMI患者PCI术后预后不良的影响因素;建立受试者工作特征(ROC)曲线评价血清CXCR7、SGK1水平对AMI患者PCI术后预后不良的预测价值。结果与健康对照组比较,AMI组血清CXCR7水平降低,SGK1水平升高(t/P=9.613/<0.001、9.955/<0.001);100例AMI患者PCI术后1年不良预后发生率为30.00%(30/100);与预后良好亚组比较,预后不良亚组血清CXCR7水平降低,SGK1水平升高(t/P=6.254/<0.001、5.329/<0.001)。多因素Logistic回归显示,Gensini评分高、KILLIP分级≥Ⅲ级、SGK1升高为AMI患者PCI术后预后不良的独立危险因素[OR(95%CI)=1.071(1.025~1.119)、4.501(1.172~17.282)、1.132(1.046~1.224)],CXCR7升高为独立保护因素[OR(95%CI)=0.956(0.926~0.987)]。血清CXCR7、SGK1及二者联合预测AMI患者PCI术后预后不良的AUC分别为0.794、0.779、0.902,二者联合的AUC大于血清CXCR7、SGK1单独预测(Z/P=3.062/0.002、2.930/0.003)。结论AMI患者血清CXCR7水平降低、SGK1水平升高,是PCI术后不良预后的影响因素,二者联合对其预测价值较高。

血清CXCL12和CXCR7在脑梗死后血管性认知功能障碍患者中的检测价值分析

目的探讨血清趋化因子配体12(CXCL12)和趋化因子受体7(CXCR7)在脑梗死后血管性认知功能障碍(VCI)患者中的检测价值。方法选取我院2021年2月至2023年2月收治的176例脑梗死患者作为研究组,根据有无发生VCI分为VCI组(47例)和非VCI组(129例),另选取同期在本院体检,且一般资料与研究组患者相匹配的176例健康者作为对照组。采用Spearman法分析脑梗死患者血清CXCL12、CXCR7表达水平与MoCA评分的相关性,Logistic回归分析影响脑梗死患者发生VCI的相关因素,受试者工作特征(ROC)曲线分析血清CXCL12和CXCR7对脑梗死后VCI的诊断价值。结果脑梗死患者血清CXCL12和CXCR7表达水平显著高于对照组,且VCI组二者表达水平均高于非VCI组(P<0.05);脑梗死患者血清CXCL12和CXCR7表达水平均与MoCA评分呈负相关(r=-0.857、-0.873,均P<0.05);VCI组和非VCI组年龄、临床类型比较,差异有统计学意义(P<0.05);年龄、临床类型、CXCL12、CXCR7为脑梗死患者发生VCI的危险因素(P<0.05);血清CXCL12和CXCR7单独检测诊断脑梗死后VCI的曲线下面积(AUC)分别为0.730、0.814,二者联合检测的AUC为0.871,优于单独检测(Z_(二者联合-CXCL12)=3.888、Z_(二者联合-CXCR7)=2.249,P=0.000、0.024)。结论血清CXCL12和CXCR7表达水平与脑梗死后VCI的发生密切相关,二者联合对脑梗死后VCI具有较高的诊断价值。

趋化因子受体CCR7在不同类型肺癌组织中的表达

目的探讨趋化因子受体CCR7在不同类型肺癌组织中的表达。方法选取2019年6月-2023年6月在本院就诊的59例NSCLC患者作为研究对象,采用免疫组化方法检测不同地区及不同病理类型肺癌组织中CCR7的表达。SPSS 17.0统计软件进行数据分析。结果免疫组化:肺癌组织中CCR7的表达明显高于正常肺组织;不同地区及病理类型肺癌组织中均表达CCR7,其中宣威及个旧地区肺癌组织中CCR7的表达较其他地区肺癌明显升高,差异有统计学意义(P<0.05);宣威地区与个旧地区肺癌组织中CCR7的表达无明显差异;CCR7的表达与淋巴结转移有关,CCR7的表达与肺癌病理类型无关。结论CCR7在肺癌组织中是高表达,CCR7的表达存在地域差异,其表达与淋巴结转移有关,与肺癌病理类型无关。

CXCR7对HeLa细胞增殖、粘附和侵袭能力的影响

基质细胞衍生因子-1(SDF-1)在肿瘤侵袭、转移过程中起着重要的调控作用.此前认为SDF-1是通过其唯一受体CXCR4来起作用.近年来发现SDF-1还有另一作用受体——CXCR7,SDF-1/CXCR7在部分肿瘤侵袭转移过程中起重要作用,但其在宫颈癌HeLa细胞中的作用目前尚未明确.通过Western blotting检测HeLa细胞中CXCR4和CXCR7的表达,阻断CXCR4或CXCR7后,通过MTT法评价细胞增殖能力,细胞粘附实验评价细胞粘附能力,Transwell实验评价细胞侵袭能力.结果表明,CXCR4和CXCR7在HeLa细胞中表达.阻断CXCR4或CXCR7后,SDF-1诱导的HeLa细胞增殖、侵袭和与内皮细胞的粘附能力均被阻断.结果提示CXCR7在SDF-1诱导HeLa细胞增殖、侵袭和与内皮细胞的粘附过程中起着重要作用,将有望成为治疗宫颈癌转移的新靶点.

大肠癌中CCR7、L-selectin、CD44v6和MMP9表达及其与淋巴转移的关系

目的探讨CC趋化因子受体7(CCR7)、L-selectin、CD44v6和MMP9在大肠癌组织中的表达及其与大肠癌淋巴转移的关系。方法采用免疫组化PV 9000两步法检测104例大肠癌组织(大肠癌组)、55例癌旁正常组织(癌旁组)和34例转移灶组织(转移组)中CCR7和L-selectin、CD44v6和MMP9的表达。结果大肠癌组、转移组中CCR7、L-selectin、CD44v6和MMP9阳性率明显高于癌旁组(P<0.05),有淋巴结转移者明显高于无转移者(P<0.05);CCR7与L-selectin、MMP9表达呈正相关(P<0.05);CD44v6与L-selectin、MMP9表达相关;L-selectin与MMP9的表达呈正相关。结论 CCR7、L-selectin、CD44v6和MMP9在大肠癌中的表达与大肠癌的发生、淋巴转移有关,它们可能共同参与了大肠癌发生及淋巴结转移过程。

口腔鳞癌中趋化因子受体CXCR4和CCR7表达及其与临床病理特征的关系

目的检测CXC类趋化因子受体4(chemokine CXC motif receptor 4,CXCR4)和CC类趋化因子受体7(chemokine CCmotif receptor 7,CCR7)在口腔鳞癌(oral squamous cell carcinoma,OSCC)中表达,探讨其与OSCC临床病理特点及颈淋巴结转移的关系。方法采用免疫组化和反转录聚合酶链反应(RT-PCR)检测64例OSCC组织原发灶、39例转移淋巴结组织和10例正常口腔黏膜组织中CXCR4及CCR7的表达,并分析其与临床病理参数的关系。结果 OSCC组织细胞中CXCR4、CCR7蛋白的阳性表达率分别为62.5%、65.6%,明显高于正常口腔黏膜组织细胞(P<0.01),其中有淋巴结转移组表达率分别为74.36%、84.62%,无淋巴结转移组表达率分别为44%、36%,差异均有统计学意义(P<0.05),而CXCR4、CCR7在淋巴结转移灶中的阳性表达率差异无统计学意义(P>0.05)。RT-PCR检测结果也证实,CXCR4及CCR7在OSCC细胞中均有阳性表达。此外,CXCR4及CCR7的表达与肿瘤的分化程度、侵袭程度和TNM分期密切相关(P<0.05),而与年龄、性别和肿瘤大小无关(P>0.05)。结论趋化因子受体CXCR4、CCR7的表达与OSCC侵袭发展和淋巴结转移密切相关。CXCR4、CCR7有可能成为OSCC治疗的新靶点。

CXCR7/CXCL12对人乳腺癌细胞侵袭和黏附能力的影响

目的探讨趋化因子受体CXCR7及其配体CXCL12对人乳腺癌细胞MDA-MB-435s移动性、侵袭能力以及黏附能力的影响。方法运用RNA干扰技术,沉默人乳腺癌细胞MDA-MB-435s CXCR7基因的表达,分别用RT-PCR、Western blot检测CXCR7 mRNA及蛋白表达水平;划痕实验检测细胞移动性的变化;Transwell小室侵袭实验检测细胞侵袭能力的变化;黏附实验检测肿瘤细胞与细胞外基质的黏附能力。结果有效沉默CXCR7的表达后,与空白对照组比较,CXCR7 mRNA及蛋白表达水平均明显降低(P<0.05),CXCL12诱导的人乳腺癌细胞移动速度减慢,侵袭能力和黏附能力明显减弱(P<0.05)。结论CXCR7表达的改变能够调节人乳腺癌细胞移动性、侵袭和黏附能力。CXCL12/CXCR7生物轴在乳腺癌的侵袭转移过程中可能具有重要作用。

趋化因子受体7(CXCR7)在食管鳞形细胞癌组织中的表达及其临床意义

目的探讨趋化因子受体7(chemokine receptor 7,CXCR7)在食管鳞癌组织中的表达情况,分析其与患者临床病理特征及预后的关系。方法选择2006年在复旦大学附属中山医院胸外科行胸段食管鳞癌根治术患者的手术切除标本共154例,同时选取49例正常食管鳞形上皮组织标本做对照。利用免疫组织化学染色方法检测肿瘤组织及正常食管鳞形上皮组织中CXCR7蛋白的表达情况,分析CXCR7表达水平与患者临床病理特征及预后的关系。结果正常食管鳞形上皮组织中的CXCR7蛋白阳性表达率为6.1%(4/49),肿瘤组织中的CXCR7阳性表达率为76.0%(116/154);CXCR7表达水平与肿瘤浸润深度、淋巴结转移及pTNM分期密切相关,差异有显著统计学意义(P<0.01)。单因素分析结果显示,患者性别、年龄、肿瘤浸润深度、淋巴结转移、pTNM分期及CXCR7表达水平与患者预后密切相关,差异有统计学意义(P<0.05);多因素分析结果显示pTNM分期和CXCR7表达水平是患者独立不良预后因素。结论 CXCR7表达水平与食管鳞癌患者复发、转移及预后密切相关,推测CXCR7在食管鳞癌发生及发展过程中起非常重要的作用。

CCR7在多发性骨髓瘤中的表达及其与髓外病变的关系

目的:检测趋化因子受体-7(CC-chemokine receptor 7,CCR7)在多发性骨髓瘤中的表达水平,探讨其与疾病特征的关系。方法:采用流式细胞术测定53例新诊断的多发性骨髓瘤患者的骨髓浆细胞CCR7的表达水平,分析其与年龄、性别、M蛋白、外周血细胞计数、血生化指标、骨髓浆细胞比例、免疫表型特点、溶骨改变、髓外病变等疾病特征的关系。结果:53例多发性骨髓瘤患者中CCR7阳性者24例,阳性率为45.28%,CCR7阳性组髓外病变发生率高于CCR7阴性组(29.17%vs 3.45%)(P<0.05)。结论:CCR7在多发性骨髓瘤中表达较高,其高表达与髓外病变发生相关,CCR7可能是预测多发性骨髓瘤发生髓外病变的重要指标。

趋化因子受体CXCR7对人乳腺癌细胞生长、凋亡及细胞周期的影响

目的通过构建CXCR7短发夹状RNA(short hairpin RNA,shRNA)序列的真核表达载体,探讨趋化因子受体CXCR7对人乳腺癌细胞MDA-MB-435s增殖、凋亡、周期的影响。方法针对CXCR7构建编码shRNA序列的重组表达载体;分别用RT-PCR和Westernblot检测CXCR7mRNA及蛋白表达水平;MTT法检测细胞增殖;TUNEL法检测细胞凋亡;流式细胞术检测细胞周期。结果构建针对CXCR7短发夹状RNA序列的表达载体,经酶切及测序证实与设计完全一致;将2个CXCR7shRNA载体(CXCR7-shRNA1;CXCR7-shRNA2)转染MDA-MB-435s细胞后,CXCR7mRNA及蛋白平均降低;抑制CXCR7的表达后,CXCR7-shRNA组细胞增殖率明显下降(P<0.05),细胞凋亡增多(P<0.05),细胞周期无明显改变。结论重组表达载体CXCR7-shRNA1、CXCR7-shRNA2能有效抑制靶基因CXCR7的表达,进而可抑制人乳腺癌MDA-MB-435s细胞的增殖,促进细胞凋亡,而对细胞周期无明显影响。

S1P受体激动剂FTY720干扰孕鼠体内DC分布从而诱导妊娠免疫耐受

目的探讨S1P受体激动剂FTY720在降低自然流产模型孕鼠胚胎丢失率进程中的作用及其可能的机制。方法以自然流产模型孕鼠为研究对象,观察腹腔注射FTY720对自然流产模型孕鼠胚胎丢失率的影响,RT-PCR检测DC表面S1PR的表达,流式细胞术及免疫组化检测孕鼠外周血及局部组织中DC数量、成熟度及其表面相应趋化因子CCL19及其受体CCR7的表达情况,趋化实验验证FTY720对DC细胞趋化能力的影响。结果 1)FTY720对正常妊娠模型孕鼠的胚胎丢失率无明显影响(P<0.05),过继转移FTY720能明显降低自然流产模型孕鼠的胚胎丢失率(P<0.05);2)DC表面存在S1P受体的广泛表达,S1P受体激动剂FTY720减少了DC表面趋化因子及其受体的表达(P<0.05),致使趋化至母胎界面DC的数量显著减少(P<0.05);3)FTY720对DC细胞的分化及凋亡率均无明显影响(P>0.05)。结论 FTY720可能通过下调DC表面趋化因子受体CCR7的表达而使趋化至母胎界面的DC数量减少,最终诱导母胎免疫耐受。

CXCR4和CCR7在Barrett's食管、食管腺癌和食管鳞癌中的表达及其临床意义

目的:探讨Barrett's食管(BE)、食管腺癌(EADC)和食管鳞癌(ESCC)中趋化因子受体4(CXCR4)和趋化因子受体7(CCR7)表达的临床意义.方法:应用免疫组织化学SP法对56例正常食管黏膜、80例BE(含22例BE伴多灶性非典型增生)、25例EADC和48例ESCC中的CXCR4和CCR7的表达进行检测,运用免疫组织化学图像分析加以定量,然后进行统计学分析.结果:CXCR4和CCR7在BE、EADC和ESCC中的表达均显著高于正常食管黏膜组织(CXCR4:78.75%,68.00%,83.33%vs39.29%;CCR7:60.00%,60.00%,58.33%vs30.36%;均P<0.01);CXCR4和CCR7的表达在BE、EADC和ESCC这3类食管病理类型中的表达无差异;CXCR4的表达在BE和ESCC中均显著高于CCR7(P<0.05,P<0.01).并且CXCR4和CCR7的表达差异与临床病理特征有一定关系;CXCR4和CCR7在BE、EADC和ESCC的表达与性别、年龄、病变发生位置均无关;CXCR4和CCR7的表达在BE无非典型增生和BE伴多灶性非典型增生这两类组织样本中无差异;CXCR4和CCR7在中-低分化EADC中的表达较高分化,以及有淋巴结转移较无淋巴结转移均显著升高(P<0.05);CXCR4和CCR7在ESCC中的表达水平在肿瘤TNM分期的Ⅲ-Ⅳ级较Ⅰ-Ⅱ级以及有淋巴结转移较无淋巴结转移均显著升高(P<0.05),中-低分化较高分化则极显著升高(P<0.01).BE无非典型增生、BE伴多灶性非典型增生和EADC组织中CXCR4的表达与CCR7的表达呈明显的正相关(r=0.456,r=0.652,r=0.490),而在ESCC中CXCR4的表达与CCR7的表达无相关性(r=0.076).结论:联合检测CXCR4和CCR7有助于更准确诊断BE、EADC和ESCC;CXCR4和CCR7高表达是EADC和ESCC具有较强浸润和转移潜能的重要标志;CXCR4和CCR7可能共同参与了从BE到EADC的发展过程.