CXCL12，CXCR4及CXCR7表达检测对乳腺癌患者疾病预后意义探讨

目的：探讨乳腺癌患者肿瘤组织中CXCL12,CXCR4和CXCR7 mRNA表达情况在肿瘤转移和疾病预后中的价值。方法采用定量PCR方法检测115例乳腺癌,临近正常组织及乳腺癌肿瘤转移患者颈部淋巴结样本中CXCL12,CXCR4和CXCR7 mRNA表达情况。随访资料采用Kaplan-Meier生存分析,对影响生存质量的因素进行多重变量Cox回归分析。结果与正常组织相比,乳腺癌组织中CXCR4和CXCR7表达明显增加,差异均有统计学意义（P﹤0.001）,两种组织中CXCL12的表达差异无统计学意义（P﹥0.05）;CXCL12在肿瘤原发部位和淋巴结转移部位的表达差异有统计学意义（P﹤0.05）,转移瘤的CXCR4和CXCR7表达均增加（P﹤0.05）。Kaplan-Meier生存分析结果表明,与CXCR4和CXCR7低表达患者相比,高表达患者的总生存率较低（P﹤0.05）。Cox回归模型显示,CXCL12、CXCR4和CXCR7表达均为影响乳腺癌患者生存情况的独立因素。结论本研究结果表明CXCL12、CXCR4和CXCR7 mRNA表达在乳腺癌患者肿瘤发展和转移中发挥重要作用,可以作为乳腺癌患者疾病预后的生物标志物。     

CXCL12及受体CXCR4在卵巢上皮性癌中的表达及其临床意义

目的:探讨趋化因子CXCL12及其受体CXCR4在卵巢上皮性癌组织中的表达及与临床病理特征和预后的关系。方法:采用免疫组织化学SP法检测6例正常卵巢表面上皮、44例卵巢上皮性癌原发灶和30例相应大网膜转移灶组织中的CXCL12和CXCR4蛋白表达。结果:正常卵巢表面上皮无CXCL12和CXCR4蛋白表达;卵巢上皮性癌原发灶的CXCL12和CXCR4表达阳性率分别为91%和59%。CXCL12表达强度与术中腹水量有显著相关性(P=0.014)。难治复发组的CXCR4阳性率(81%)显著高于无复发组(28%,P<0.001)。单因素分析显示:CXCR4阳性表达的患者中位数肿瘤无进展生存时间和总生存时间(15个月、27个月)明显短于CXCR4阴性表达者(>21个月、>32个月,分别为P<0.001和P=0.017)。多因素分析显示:CXCR4表达和残余灶大小是影响卵巢上皮性癌患者的肿瘤无进展生存时间和总生存时间的独立预后因素。结论:CXCR4在卵巢上皮性癌中的表达阳性率较高,是影响其预后的独立指标之一。     

趋化因子CXCL12及其受体CXCR4与乳腺癌

 趋化因子CXCL12及其受体CXCR4在乳腺癌发生发展的多个过程中受到多种因素调控并表达,并且多项研究证实CXCL12及CXCR4不但有助于判断乳腺癌患者的预后,而且针对CXCR4的治疗更为乳腺癌患者提供了新的联合治疗方案,给患者更为理想的治疗。     

CXCL12- CXCR4在乳腺浸润性导管癌中的表达及临床意义

目的：研究乳腺浸润性导管癌中趋化因子 CXCL12及其对应的特异趋化因子受体 CXCR4的表达,分析其与浸润性导管癌临床病理学特征的关系。方法：用免疫组化法研究200例乳腺浸润性导管癌中 CX-CL12、CXCR4的表达情况,并探讨二者单一表达或共表达与临床病理因素的相关性。结果：CXCL12在40%（80/200）浸润性乳腺癌中阳性表达,其与 TNM 分期和肿瘤大小相关（P <0.05）;CXCR4在48%（96/200）浸润性乳腺癌中阳性表达,其表达与浸润性乳腺癌的 TNM 分期相关（P <0.05）。CXCL12与 CXCR4共表达于29%（58/200）的浸润性乳腺癌,二者的共表达与 TNM 分期和淋巴结转移情况相关（ P <0.01）。结论：CX-CL12与 CXCR4共表达很可能是协同乳腺浸润性导管癌进展及淋巴结转移的重要因素,检测 CXCL12与 CX-CR4共表达比检测 CXCL12或 CXCR4单一分子标记更有意义。     

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。     

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。     

CXCL12/CXCR4信号通路对肿瘤的作用及机制的研究进展

随着环境污染的加剧和老龄社会的来临,肿瘤的发病率不断升高,对肿瘤诊治的研究有十分重要的意义.目前,对肿瘤的诊治的研究也进入了分子水平,CXCL12/CXCR4信号通路对多种肿瘤的生物学行为有重要的影响,对其进行研究也是近年来的热点.本文将对CXCL12/CXCR4信号通路对肿瘤的作用及机制进行综述.     

宫颈腺癌细胞CXCR4/CXCL12过表达与淋巴结转移和慢性炎症的关系

背景与目的:CXCL12是一种炎症趋化因子,CXCR4是其特异性受体.有文献报道CXCR4参与多种恶性肿瘤的转移过程.但CXCR4/CXCL12在宫颈腺癌细胞中表达的意义鲜见报道.本研究探讨CXCR4/CXCL12在宫颈腺癌细胞中过表达与淋巴结转移及宫颈慢性炎症程度的相关性.方法:收集35例行子宫颈癌根治术的Ⅰ B1～ⅡB期宫颈腺癌标本,其中有淋巴结转移组8例,无淋巴结转移组27例.组织切片行CXCR4和CXCL12免疫组化染色及HE染色,90%以上肿瘤细胞强着色定义为过表达.采用Fisher's精确概率检验法、卡方检验及Pearson相关检验分析结果.结果:35例均有不同数量肿瘤细胞表达CXCR4.有淋巴结转移组CXCR4过表达率(62.50%,5/8)高于无淋巴结转移组(22.00%,6/27),P＜0.05.临床Ⅰ B期有淋巴结转移组CXCR4过表达率(33.33%,1/3)高于无淋巴结转移组(26.01%,6/23),但P＞0.05;临床ⅡB期,有淋巴结转移组CXCR4过表达率高于无淋巴结转移组(80.00%,4/5 vs.0.00%,0/4),P＜0.05.CXCR4过表达预测淋巴结转移的阳性预测值为45.45%,阴性预测值为87.50%.35例中33例有数量不等的肿瘤细胞表达CXCL12.无论有淋巴结转移组或无淋巴结转移组,临床Ⅱ期病例CXCL12过表达率均明显高于I B期(0.00% vs.80.00%,21.73% vs.75.00%),P＜O.05.23例临床Ⅰ B期无淋巴结转移组,CXCR4过表达率与CXCL12过表达率呈正相关(P＜0.05):但在Ⅰ B期有淋巴结转移组(3例)及ⅡB期(9例)病例组,两者间无相关性.35例病例均伴有不同程度慢性炎症,炎性浸润主要为淋巴细胞.CXCL12过表达率与宫颈慢性炎症浸润程度无相关性,P＞0.05.结论:宫颈腺癌细胞CXCR4过表达提示具有较高淋巴结转移潜能.随着肿瘤进展,CXCL12过表达率也随之升高.宫颈腺癌中慢性炎症细胞可能由其它趋化因子吸引所致,而非CXCL12.     

CXCL12-CXCR4/CXCR7生物轴在肝癌中的研究进展北大核心CSCD

肝细胞癌(hepatocellular carcinoma,HCC)是世界上发病率和死亡率最高的恶性肿瘤之一。研究发现,CXCL12-CXCR4/CXCR7生物轴可通过自分泌和(或)旁分泌机制调控HCC细胞的生长、血管生成、免疫逃逸及侵袭转移等关键步骤,有可能成为HCC防治新靶点和预后评价新标志。本文就当前国内外研究CXCL12-CXCR4/CXCR7生物轴在肝癌发生和发展过程中的作用以及与此相关的信号转导途径进行综述。     

大肠癌CXCR4表达及其与预后的关系

[目的]探讨CXCR4在大肠癌中的表达情况及其与预后的关系。[方法]采用SP免疫组化方法检测70例大肠癌组织和14例癌旁组织中CXCR4蛋白的表达。[结果]CXCR4蛋白在大肠癌组织中阳性表达率为57.1%（40/70）,显著高于癌旁组织的14.3%（2/14）（P〈0.01）。CXCR4阳性表达与大肠癌的Duke分期（P=0.041）、淋巴结转移（P=0.018）显著相关。CXCR4阴性表达者的无瘤生存率显著优于阳性表达者（P=0.008）。[结论]CXCR4蛋白在大肠癌中过度表达与大肠癌的发生发展和预后相关。     

CXCL12/CXCR4 and breast cancer

CXCL12 and its receptor CXCR4 can express in breast cancer, and are regulated by several factors in the genesis and development of breast cancer. Lots of researches have proved that CXCL12 and CXCR4 can be used as new independent prognostic makers of breast cancer. Treatment targeted for CXCR4 can be seen as a new kind of combination therapy, which may provides patients a more ideal treatment.     

CXCL12-CXCR4生物学轴在胰腺癌中的表达及其与血管生成的相关性

肿瘤转移是一个复杂的、非随机的多步骤过程,肿瘤细胞的运动迁移、黏附、生长、新血管生成、特异性转移器官的归巢和逃避免疫等关键步骤.近年来的研究显示,趋化因子CXCL12与其特异性受体CXCR4所构成的CXCL12-CXCR4生物学轴,在多种肿瘤的播散和器官特异性转移中发挥重要作用.     

Expression of CXCL12 and its receptor CXCR4 correlates with lymph node metastasis in submucosal esophageal cancer

BACKGROUND AND OBJECTIVES: The chemokine CXCL12 and its receptor CXCR4 are involved in cell migration, proliferation, and angiogenesis, and promote organ-specific localization of distant metastases in various carcinomas. We examined their expression and microvessel density (MVD) in submucosal esophageal squamous cell carcinoma (ESCC) and analyzed their connection to clinicopathological findings including lymph node micrometastasis (LMM). METHODS: Eighty-six patients with submucosal ESCC underwent curative resection from 1985 to 2002. Immunohistochemical staining of CXCL12, CXCR4, and CD34 was performed with primary tumors, and staining of cytokeratin was performed with dissected lymph nodes. MVD was calculated from CD34 expression, and LMM detected by cytokeratin staining. RESULTS: Expression of CXCL12, but not CXCR4, correlated with lymph node metastasis. There was no significant correlation between the expression of CXCL12 and/or CXCR4 and MVD. LMM was detected in 8 cases and 14 lymph nodes. CXCL12 expression and high MVD were found in tumors with lymph node metastasis including LMM. Furthermore, in the CXCR4-positive tumors, positive CXCL12 expression was more significantly correlated with lymph node metastasis and/or LMM than negative CXCL12 expression. CONCLUSIONS: Evaluation of CXCL12 and CXCR4 expression should assist detection of lymph node metastasis including LMM in submucosal ESCC.     

CXCR4/CXCL12 expression and signalling in kidney cancer

CXCL12 (SDF-1), a CXC-chemokine, and its specific receptor, CXCR4, have recently been shown to be involved in tumourgenesis, proliferation and angiogenesis. Therefore, we analysed CXCL12alpha/CXCR4 expression and function in four human kidney cancer cell lines (A-498, CAKI-1, CAKI-2, HA-7), 10 freshly harvested human tumour samples and corresponding normal kidney tissue. While none of the analysed tumour cell lines expressed CXCL12alpha, A-498 cells were found to express CXCR4. More importantly, real-time RT-PCR analysis of 10 tumour samples and respective adjacent normal kidney tissue disclosed a distinct and divergent downregulation of CXCL12alpha and upregulation of CXCR4 in primary tumour tissue. To prove that the CXCR4 protein is functionally active, rhCXCL12alpha was investigated for its ability to induce changes of intracellular calcium levels in A-498 cells. Moreover, we used cDNA expression arrays to evaluate the biological influence of CXCL12alpha. Comparing gene expression profiles in rhCXCL12alpha stimulated vs unstimulated A-498 kidney cancer cells revealed specific regulation of 31 out of 1176 genes tested on a selected human cancer array, with a prominent stimulation of genes involved in cell-cycle regulation and apoptosis. The genetic changes reported here should provide new insights into the developmental paths leading to tumour progression and may also aid the design of new approaches to therapeutic intervention.     

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.     

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...     

Adenosine upregulates CXCR4 and enhances the proliferative and migratory responses of human carcinoma cells to CXCL12/SDF-1alpha

The level of expression of the chemokine receptor CXCR4 has been shown to play a crucial role in determining the ability of cancer cells to metastasize from the primary tumor and become established in tissue sites that are rich in the CXCR4 ligand CXCL12/SDF-1alpha. High CXCR4 expression on cancer cells is associated with an increased risk of recurrence and poorer overall survival. We propose that local tissue mediators within the primary tumor or at secondary sites may modulate the level of CXCR4 expression and, therefore, potentially affect the ability of the cancer cells to metastasize. The purine nucleoside adenine-9-beta-D-ribofuranoside (adenosine) is generated at high concentrations within the extracellular fluid of solid tumors because of their hypoxia. We show here that adenosine acts through A(2A) and A(2B) adenosine receptors on human colorectal carcinoma cells to upregulate CXCR4 mRNA expression up to 10-fold and selectively increases cell-surface CXCR4 protein up to 3-fold. This increase in cell-surface CXCR4 enables the carcinoma cells to migrate toward CXCL12, and enhances their proliferation in response to CXCL12. Adenosine may therefore be one of the factors within the tumor microenvironment that facilitates tumor dissemination, by upregulating CXCR4 on certain cancer cells and enhancing cellular responses to CXCL12.