趋化因子受体CXCR4/CXCL12信号转导通路与胃癌淋巴结转移关系的研究

目的：检测趋化因子受体CXCR4/CXCL12信号转导通路在胃癌组织、远癌正常粘膜以及转移淋巴结中的表达情况,分析CXCR4/CXCL12在胃癌淋巴结转移中的作用。方法：应用Westernblot检测胃癌组织中CXCR4/CXCL12通路成员表达。结果：胃癌组织中CXCR4/CXCL12表达水平明显高于正常胃粘膜（P〈0.05）;32例淋巴结转移癌组织中22例CXCR4/CXCL12蛋白表达高于原发癌;CXCR4/CXCL12表达水平与淋巴结转移有关（P（0.05）。结论：趋化因子受体CXCR4/CXCL12在原发胃癌及其淋巴结转移癌组织中均呈高表达,CXCR4信号转导通路可能在胃癌淋巴结转移过程中起重要作用。     

CXCL12/CXCR4轴与乳腺癌研究进展

趋化因子CXCL12与其受体CXCR4信号通路与乳腺癌细胞的定向播散和器官特异性转移密切相关,研究CXCL12/CXCR4轴在乳腺癌生长及转移中的重要作用,有望为乳腺癌靶向治疗提供新的策略。     

结直肠癌CXCL12-CXCR4/CXCR7轴作用机制研究进展

目的 探讨趋化因子CXCL12及其受体与结直肠癌的关系,以总结最新研究进展。方法 应用PubMed、Web of Science数据库和中国期刊全文数据库(CNKI)检索系统,以“结直肠癌、CXCL12、CXCR4、CXCR7、靶向治疗和趋化因子等”为中文关键词,以“colorectal cancer、CXCL12、CXCR4、CXCR7、targeted therapy、chemokines”等为英文关键词,检索2010-01-01-2022-03-31的相关文献,共检索到中文文献76篇,英文文献256篇。纳入标准：(1)结直肠癌发生时CXCL12、CXCR4和CXCR7表达水平变化;(2)CXCL12-CXCR4/CXCR7轴对结直肠癌发生发展的影响及作用机制;(3)靶向干预CXCL12-CXCR4/CXCR7轴对结直肠癌的影响及相关临床研究。排除标准：结直肠癌与非CXCL12/CXCR4或CXCL12/CXCR7信号轴。最终共纳入分析文献56篇,中文16篇,英文40篇。结果 CXCL12及其受体在结直肠癌组织及常见转移部位表达显著升高,相关分子信号可通过CXCL12-CXCR4/...     

CXCR4/CXCL12轴与白血病复发

趋化因子受体CXCR4与其特异性配体CXCL12结合,启动下游信号通路形成CXCR4/CXCL12生物轴,在造血干细胞的归巢、再植以及维持正常造血和造血微环境的稳定过程中发挥重要作用.CXCR4/CXCL12轴同时也可促进白血病细胞存活、增殖、转移及耐药,与白血病髓内外复发关系密切.CXCR4的表达水平可作为判断白血病...     

趋化因子及其受体与肿瘤

趋化因子及其受体在肿瘤的发生、生长和转移等各个阶段都有复杂的网络性表达,研究表明趋化因子CXCL12及受体CXCR4介导乳腺癌、结肠癌、膀胱癌和前列腺癌等肿瘤的转移和发展,这为深入探讨肿瘤的发病及转移机制提供了新视角。现对近年来有关趋化因子及其受体与肿瘤之间的研究进展作一综述。     

趋化因子受体CXCR7及其与肿瘤的关系

CXCR7是继CXCR4之后发现的趋化因子CXCL12的新受体.目前研究表明,CXCL12/CXCR7生物轴对多种肿瘤的发展有重要影响,与CXCL12/CXCR4生物轴的作用有一定相似性.CXCR7广泛表达于多种肿瘤组织及肿瘤细胞,在肿瘤细胞的生长增殖、黏附迁徙中起重要作用.抑制CXCR7表达或阻断其信号传导通路可能为肿瘤治疗提供新策略.     

趋化因子及其受体与肿瘤

趋化因子及其受体在肿瘤的发生、生长和转移等各个阶段都有复杂的网络性表达，研究表明趋化因子CXCL12及受体CXCR4介导乳腺癌、结肠癌、膀胱癌和前列腺癌等肿瘤的转移和发展，这为深入探讨肿瘤的发病及转移机制提供了新视角。现对近年来有关趋化因子及其受体与肿瘤之间的研究进展作一综述。     

胰腺癌CXCL12/CXCR4通路研究进展

目的:总结CXCL12/CXCR4生物学轴与胰腺癌侵袭和转移关系的研究现状.方法:应用PubMed及CNKI期刊全文数据库检索系统,以“CXCL12、CXCR4和胰腺癌”等为关键词,检索2005-2011年的相关文献,共检索到中文文献56条,英文文献152条.纳入标准:1)CXCL12-CXCR4生物学轴的生物学特性及功能;2)CXCL12/CXCR4生物学轴与肿瘤发生、发展的关系;3)CXCL12/CXCR4生物学轴信号转导通路的相关调控因子及其调节机制;4)CXCL12/CXCR4生物学轴在胰腺癌侵袭、转移中的作用及其机制;5)CXCL12/CXCR4生物学轴与胰腺癌的治疗及预后.根据纳入标准共采用中文文献3条,英文文献17条.结果:趋化因子受体CXCR4与其配体CXCL12结合组成的生物学轴具有高度特异性,在胰腺癌细胞的黏附、侵袭、转移、增殖和生存中发挥重要作用,与细胞外基质降解、胰腺癌血管、淋巴管生成及嗜神经侵袭密切相关,并受相关因子调控影响其信号转导通路.结论:CXCL12/CXCR4生物学轴在胰腺癌发生、发展中发挥着重要作用,有望成为胰腺癌靶向治疗的新靶点,但其具体作用的相关转导通路和调节机制还未完全明确,有待进一步研究.     

CXCR4和CXCR7在肿瘤中的研究进展

以往的研究认为趋化因子受体4(chemokine receptor 4,CXCR4)是趋化因子CXCL12的唯一受体,CXCL12/CXCR4生物轴在肿瘤发展过程中起重要作用,然而最近研究发现CXCL12尚存在CXCR7这一新的受体,并且CXCL12/CXCR7生物轴同样对肿瘤的发生发展起重要作用.本文就有关趋化因子受体CXCR4和CXCR7在肿瘤中的表达、促进肿瘤增殖和转移、促进血管新生以及肿瘤治疗等方面的研究作一综述.     

CXCL12／CXCR4生物轴与消化系统恶性肿瘤

消化系统恶性肿瘤发病率及死亡率均远远高于其它系统恶性肿瘤，对消化系统恶性肿瘤的预防和治疗研究亟待进一步深入。细胞移位是相当多病理生理过程的基本步骤，包括恶性肿瘤细胞的生长及转移。越来越多地研究认为肿瘤细胞通过化学趋化因子及其相应受体介导的化学趋化机制调节其生长和转移，趋化因子在恶性肿瘤中具有多方面作用，归纳为：①诱导白细胞向肿瘤组织浸润，调节免疫功能，尤其是肿瘤相关的巨噬细胞、T细胞和树突状细胞；②引导肿瘤细胞迁移到特定部位；③调节血管生成；④直接活化肿瘤细胞，调控其恶性肿瘤相关的功能表现。近年研究发现，趋化因子CXCL12及其受体CXCR4构成的生物轴在包括乳腺癌在内的多种实体瘤的生长、转移中发挥重要作用。CXCL12／CXCR4生物轴与消化系统恶性肿瘤之间关系密切，CXCL12的刺激促进CXCR4的表达及消化系统恶性肿瘤的转移；CXCR4持续高表达预示肿瘤的复发及预后不良；在CXCL12作用下，肿瘤细胞黏附／迁移和增殖能力亦显著增强，这些效应被CXCR4的抗体所拮抗。未来研究寄希望通过拮抗影响肿瘤转移的CXCL12与CXCR4等趋化因子及其受体的作用来阻断消化系统恶性肿瘤转移，将可能会成为一种新的治疗消化系统恶性肿瘤的有效途径。     

Chemokine axes CXCL12/CXCR4 and CXCL16/CXCR6 correlate with lymph node metastasis in epithelial ovarian carcinoma

Recent evidence suggests that the chemokine axis of CXC chemokine ligand-12 and its receptor CXC chemokine receptor-4(CXCL12/CXCR4) is highly expressed in gynecological tumors and the axis of CXC chemokine ligand-16 and CXC chemokine receptor-6(CXCL16/CXCR6) is overexpressed in inflammation-associated tumors.This study aimed to determine the relationship between CXCL12/CXCR4,CXCL16/CXCR6 and ovarian carcinoma's clinicopathologic features and prognosis.Accordingly,the expression of these proteins in ovarian ...     

CXCL12-CXCR4在消化道肿瘤转移中的研究进展

趋化因子CXCL12及其受体CXCR4不仅表达于免疫细胞,在某些肿瘤细胞中也呈高表达.最近研究表明,其与食管癌、胃癌、结直肠癌等的转移密切相关.展开其生物学特性、在消化道肿瘤中的表达及转移相关性研究,将为消化道肿瘤转移的防治提供新的思路.     

The biological role of the CXCL12/CXCR4 axis in esophageal squamous cell carcinoma

Esophageal cancer is the eighth most common malignant tumor and the sixth leading cause of cancer-related death worldwide. Esophageal squamous cell carcinoma (ESCC) is the main histological type of esophageal cancer, and accounts for 90% of all cancer cases. Despite the progress made in surgery, chemotherapy, and radiotherapy, the mortality rate from esophageal cancer remains high, and the overall 5-year survival rate is less than 20%, even in developed countries. The C-X-C motif chemokine ligand 12 (CXCL12) is a member of the CXC chemokine subgroup, which is widely expressed in a variety of tissues and cells. CXCL12 participates in the regulation of many physiological and pathological processes by binding to its specific receptor, C-X-C motif chemokine receptor type 4 (CXCR4), where it causes embryonic development, immune response, and angiogenesis. In addition, increasing evidence indicates that the CXCL12/CXCR4 axis plays an important role in the biological processes of tumor cells. Studies have shown that CXCL12 and its receptor, CXCR4, are highly expressed in ESCC. This abnormal expression contributes to tumor proliferation, lymph node and distant metastases, and worsening prognosis. At present, antagonists and imaging agents against CXCL12 or CXCR4 have been developed to interfere with the malignant process and monitor metastasis of tumors. This article summarizes the structure, function, and regulatory mechanism of CXCL12/CXCR4 and its role in the malignancy of ESCC. Current results from preclinical research targeting CXCL12/CXCR4 are also summarized to provide a reference for the clinical diagnosis and treatment of ESCC.     

趋化因子CXCL9和CXCL10介导的胃癌免疫细胞浸润的探讨

目的:探讨不同刺激因子对胃癌中CXCL9和CXCL10表达的影响,及不同血样中免疫细胞经不同方式活化后,其膜表面CXCR3的表达情况,建立并评价CXCR3和CXCL9、CXCL10介导的靶向抗胃癌免疫治疗新技术。方法:采用IFN-γ、TNF-α、Poly（I∶C）、LPS和PHA刺激胃癌细胞（BGC-823、SGC-7901及MKN-28）,ELISA法测定肿瘤细胞分泌CXCL9和CXCL10的情况。将免疫细胞分别活化为CIK和CAPRI,流式细胞术检测活化前后免疫细胞表面CXCR3的表达情况。四甲基偶氮唑蓝（MTT）法评价刺激因子［IFN-γ、TNF-α、Poly（I∶C）、LPS和PHA］本身对肿瘤细胞增殖的影响。Transwell趋化实验比较趋化因子CXCL9和CXCL10及其受体CXCR3的表达差异对免疫细胞靶向归巢至肿瘤的数量的影响。结果:胃癌细胞株基础状态无明显CXCL9和CXCL10的表达,IFN-γ可以显著升高CXCL9和CXCL10的表达水平,TNF-α、Poly（I∶C）、LPS和PHA均可升高CXCL9和/或CXCL10的表达水平,与IFN-γ有一定的协同作用,其中Poly（I∶C）效果最强。IFN-γ、TNF-α、Poly（I∶C）、LPS和PHA等刺激因子本身在单独或联合应用时对3种肿瘤细胞均无明显增殖抑制作用。相同刺激条件下,胃癌高中分化细胞株的CXCL9和CXCL10表达显著高于低分化细胞株。CIK、CAPRI两种方式活化后细胞膜表面CXCR3显著升高。CIK、CAPRI两种活化方式刺激CXCR3的升高效能相当,无统计学差异。3种血样［健康足月新生儿脐带血、健康成人外周血单个核细胞（PBMC）、肿瘤患者PBMC］在相同活化方式刺激条件下CXCR3的表达无统计学差异。免疫活性细胞经由CXCL9、CXCL10与CXCR3介导,可以更多数量归巢至肿瘤。结论:趋化因子CXCL9和CXCL10及其受体CXCR3的高表达可以有效促进免疫细胞靶向归巢至肿瘤。     

CXCL12/CXCR4生物学轴诱导前列腺癌骨转移的作用机制研究进展

研究发现趋化因子CXCL12(Stromal-derived factor-1,SDF-1)和受体CXCR4[chemokine (C-X-C motif) receptor 4]广泛表达于组织和器官上,相关的研究发现其与前列腺癌细胞的黏附、侵袭、增殖和生存有关,并认为其在前列腺癌骨转移的发生中发挥重要作用.通过阐明CXCL12/CXCR4生物学轴和前列腺癌骨转移之间的关系,从而寻找有助于疾病治疗的新途径.     

Expression of the CXCL12/CXCR4 and CXCL16/CXCR6 axes in cervical intraepithelial neoplasia and cervical cancer

The chemokine CXCL12 is highly expressed in gynecologic tumors and is widely known to play a biologically relevant role in tumor growth and spread. Recent evidence suggests that CXCL16, a novel chemokine, is overexpressed in inflammation-associated tumors and mediates pro-tumorigenic effects of inflammation in prostate cancer. We therefore analyzed the expression of CXCL12 and CXCL16 and their respective receptors CXCR4 and CXCR6 in cervical intraepithelial neoplasia (CIN) and cervical cancer and further assessed their association with clinicopathologic features and outcomes. Tissue chip technology and immunohistochemistry were used to analyze the expression of CXCL12, CXCR4, CXCL16, and CXCR6 in healthy cervical tissue (21 cases), CIN (65 cases), and cervical carcinoma (60 cases). The association of protein expression with clinicopathologic features and overall survival was analyzed. These four proteins were clearly detected in membrane and cytoplasm of neoplastic epithelial cells, and their distribution and intensity of expression increased as neoplastic lesions progressed through CIN1, CIN2, and CIN3 to invasive cancer. Furthermore, the expression of CXCR4 was associated significantly with the histologic grade of cervical carcinoma, whereas the expression of CXCR6 was associated significantly with lymph node metastasis. In Kaplan-Meier analysis, patients with high CXCR6 expression had significantly shorter overall survival than did those with low CXCR6 expression. The elevated co-expression levels of CXCL12/CXCR4 and CXCL16/CXCR6 in CIN and cervical carcinoma suggest a durative process in cervical carcinoma development. Moreover, CXCR6 may be useful as a biomarker and a valuable prognostic factor for cervical cancer.     

CXCL12／CXCR4生物学轴诱导前列腺癌骨转移的作用机制研究进展

研究发现趋化因子CXCL12（Stromal—derived factor-1,SDF-1）和受体CXCR4[chemokine（C—X—Cmotif）receptor4]广泛表达于组织和器官上,相关的研究发现其与前列腺癌细胞的黏附、侵袭、增殖和生存有关,并认为其在前列腺癌骨转移的发生中发挥重要作用。通过阐明CXCL12／CXCR4生物学轴和前列腺癌骨转移之间的关系,从而寻找有助于疾病治疗的新途径。