CXCR1/CXCL8在结肠癌归巢性肝转移中作用的研究

目的探讨结肠癌发生器官特异性转移的规律性,研究CXCR1/CXCL8在转移性结肠癌瘤细胞归巢性肝转移中的作用。方法应用流式细胞术分析不同转移潜能结肠癌瘤细胞株、结肠癌原发灶及肝转移灶、正常结肠黏膜和肝组织中CXCR1的表达及其差别;分析CXCR1/CXCL8对肝转移性结肠癌瘤细胞CXCR1表达、瘤细胞生长、增殖性、侵袭能力、细胞骨架及定向运动能力的影响。结果Lovo、colon205胞膜CXCR1表达率分别为3.15%、6.67%;Lovo、co-lon205细胞经CXCL8刺激48h,CXCR1受体表达率50.45%和4.93%;Lovo细胞经CXCL8（75ng/ml）刺激前、后,CX-CR1表达量（ct值）为20.83和19.23;正常结肠黏膜、高分化结肠腺癌、低分化结肠腺癌中CXCR1的表达率分别为2.21%、6.65%和5.19%;正常肝组织、肝转移灶CXCR1的表达率为2.73%和22.62%;CXCL8刺激前、后Lovo细胞的增殖能力分别为3.27%和24.17%;CXCL8刺激后,Lovo细胞F-actin表现出解聚-聚合状态的改变,聚合程度呈时间性递增,高聚合状态表现在刺激后的72h;CXCR1/CXCL8作用前、后的lovo细胞侵袭数分别为74.2±13.28和6.39±1.8（P〈0.01）,趋化运动细胞数分别为89.67±6.16和18.53±5.59（P〈0.05）。结论结肠癌瘤细胞CXCR1的表达与原发灶分化程度无关;CXCL8提高肝转移性结肠癌瘤细胞CXCR1的表达,“诱导”循环瘤细胞转变为肝转移性瘤细胞;CX-CL8/CXCR1介导肝转移瘤细胞的器官特异性转移过程,使结肠癌肝转移表现出与淋巴细胞趋化性迁移相类似的归巢性转移特征。在归巢性转移过程中,CXCL8/CXCR1具有器官特异性转移谱系特征,诱导转移瘤细胞的定向运动和转移灶形成。     

趋化因子受体CXCR4及其配体CXCL12在胃癌组织中的表达及其意义

目的 探讨CXCR4/CXCL12在胃癌组织中表达及其在肝转移中的作用。方法 应用Western blot 检测40例胃癌患者标本中肿瘤组织、邻近正常黏膜以及肝转移组织中CXCR4/CXCL12通路成员的表达情况,免疫组织化学法检测CXCR4/CXCL12在细胞水平的分布。结果 胃癌组织中CXCR4/CXCL12表达水平明显增高（肿瘤组织vs正常黏膜,P<0.05）;10例肝转移组织中CXCR4/CXCL12表达增高（转移组织vs原发肿瘤,P<0.05）;CXCR4/CXCL12表达水平与TNM 分期晚（Ⅲ/Ⅳ）有关（P<0.05）。结论 CXCR4/CXCL12信号转导通路可能在胃癌肝转移过程中起一定作用,详细机制尚待进一步研究。     

聚肌胞对活化早期T细胞PD-1表达的诱导及对黑色素瘤生长的抑制作用

 目的 探讨活化早期阶段（脾组织内，未向靶器官迁移的）T细胞程序性死亡受体1（PD-1）表达情况。方法 6~8周龄C57BL/6小鼠随机分组后，以Poly I:C肽疫苗免疫，7天后获取小鼠脾细胞，观察Poly I:C对非特异性及特异性T细胞活化的影响，并检测特异性CD8⁺T细胞表面PD-1表达。同时，通过敲除CD8细胞观察Poly I:C的抗肿瘤效应是否与CD8⁺T细胞相关。结果 小鼠经Poly I:C免疫后，脾组织内非特异性及特异性T细胞活化均显著增强；活化的特异性CD8⁺T细胞虽高表达PD-1，但仍可合成T细胞功能性分子IFN-γ。此外，Poly I:C能显著抑制荷瘤小鼠黑色素瘤生长（P=0.0243），且该效应与CD8+T细胞有关。结论 Poly I:C可以促进T细胞活化；活化早期的（脾组织内）T细胞虽高表达PD-1，但仍具有功能。     

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。     

CXC趋化因子受体3变体及其配体在肿瘤微环境中作用的研究进展

恶性肿瘤是严重威胁人类生命的疾病之一,近年来免疫治疗已经成为肿瘤治疗的焦点,解决免疫治疗只对部分患者 有效的问题迫在眉睫。在肿瘤微环境（tumor microenvironment,TME）中趋化因子介导细胞的定向移动,同时具有多种调节功能, 既可以作用于免疫细胞,也可直接作用于肿瘤细胞,发挥了复杂的生物学作用。CXC趋化因子受体3（CXC chemokine receptor 3, CXCR3）通过与其同源CXC趋化因子配体9（CXC chemokine ligand 9,CXCL9）/10/11结合,不仅参与了肿瘤发生、侵袭并促进肿 瘤相关血管的形成,同时也介导了免疫细胞向肿瘤组织中浸润,为无免疫反应性或免疫反应性差的“冷肿瘤”转变为免疫反应性 的“热肿瘤”提供了新的思路,并且可能成为治疗的新靶点。这种抗肿瘤和促肿瘤的双重作用,似乎与CXCR3变体（CXCR3-A、 CXCR3-B）发挥相反的作用密切相关。本文就近年来CXCR3变体CXCR3-A、CXCR3-B及其配体CXCL9/10/11在TME中作用的 研究进展展开综述。     

趋化因子CXCL12及其受体在人前列腺癌嗜神经过程中的表达及相关机制

目的：阐述CXCL12-CXCR4在前列腺癌嗜神经过程中的作用及相关机制。方法：H＆E染色观察前列腺癌细胞对肿瘤组织及其周围神经的浸润，免疫组织化学方法检测CXCL12和CXCR4、MMP-2、MMP-9在22例人前列腺癌和20例前列腺增生组织中的表达差别，浸润神经的肿瘤细胞CXCR4和CXCL12的表达。结果：在人前列腺癌组织中，存在着较明显的肿瘤细胞侵犯神经现象，人前列腺癌组织中CXCL12、CXCR4、MMP-2和MMP-9表达阳性率均较前列腺增生组织明显升高（P〈0．05），侵犯神经的肿瘤细胞表达CXCR4，神经组织内神经鞘膜细胞表达CXCL12。结论：在前列腺癌组织中存在肿瘤细胞嗜神经现象，肿瘤肿瘤细胞分泌CXCL12，CXCR4与MMP-2、MMP-9促进了癌细胞的嗜神经浸润。     

结肠癌肝转移与CXCR1/CXCL8信号传导通路关系的研究

目的:探讨趋化因子受体与配体(CXCR1/CXCL8)信号通路在结肠癌肝转移中的作用.方法:分析高分化、非转移性结肠癌细胞株(colon205)与低分化、肝转移结肠癌细胞株(lovo)、结肠癌原发灶及肝转移灶、正常结肠黏膜及肝组织中CXCR1的表达;分析CXCR1/CXCL8对瘤细胞增殖、侵袭能力、细胞骨架及迁移的影响.结果:正常结肠黏膜、高分化与低分化结肠腺癌中CXCR1的表达率分别为2.214%、6.652%和5.198%;正常肝组织、肝转移灶CXCR1表达率为2.728%和22.62%;lovo、colon205胞膜CXCR1表达率为3.15%和6.67%;CX-CL8刺激48h,胞膜CXCR1表达率分别为50.45%和4.93%;CXCL8刺激前、后lovo细胞的增殖能力分别为3.27%和24.17%;CXCL8刺激后,lovo细胞F-actin表现出解聚-聚合状态的改变,聚合程度呈时间性递增,高聚合状态表现在刺激后的72h;CXCR1/CXCL8作用前、后的lovo细胞侵袭数分别为6.39±1.8和74.2±13.28(P<0.01),趋化运动细胞数分别为18.53±5.59和89.67±6.16(P<0.05).结论:在CXCL8作用下,肝转移瘤细胞高表达CXCR1;CXCR1/CXCL8促进肝转移瘤细胞的生长、增殖,诱导肝转移性结肠癌细胞的定向迁移,CXCR1/CXCL8信号通路在结肠癌归巢性迁移过程中发挥作用.     

CXCL12和CXCR4在食管鳞癌组织中的表达及其与预后的关系

背景与目的：新近研究显示CXCL12／CXCR4在多种肿瘤组织中有表达,并与肿瘤细胞的增殖、侵袭特性相关;本研究旨在检测CXCL12及其受体CXCR4在食管鳞癌中的表达,研究两者对食管癌预后的影响及其与临床及病理因素之间的关系。方法：收集食管癌术后标本186例及正常食管上皮组织20例（对照组）,应用免疫组化法检测食管癌组织中CXCR4与CXCL12的表达。结果：186例食管癌组织中CXCR4的表达率为67．2％,CXCL12的表达率为63．4％,20例正常食管上皮组织中无CXCR4及CXC112蛋白表达。多因素分析：PTNM分期及CXCR4的表达是影响食管癌根治术后患者预后的独立因素（P〈0．05）：CXCL12阳性组与阴性组5年生存率分别为18．8％和21．0％,差异无统计学意义（P〉0．05）。CXCR4阳性组与阴性组5年生存率分别为2．2％和28．5％。差异有统计学意义（P〈0．05）;有淋巴结转移组及病理分期T3期组CXCR4表达率较无淋巴结转移组及病理分期T1-2组高（P〈0．05）,食管癌组织中CXCR4的表达与CXCL12的表达之间无相关性。结论：CXCL12和CXCR4在食管癌组织中均有较高的表达,CXCR4的表达水平与食管肿瘤的发展及预后有一定的关系。     

结直肠癌中CXCR5、CXCL13、MMP-12和MMP-13的表达及意义

目的 观察结直肠癌组织中趋化因子CXCR5及其配体CXCL13以及MMP-12、MMP-13的表达,探讨其与临床病理特征、预后的关系。方法 应用免疫组织化学SP法检测236例结直肠癌及其切缘正常肠黏膜组织以及62例结直肠腺瘤组织中CXCR5、CXCL13、MMP-12和MMP-13蛋白表达。结果 （1）CXCR5、CXCL13、MMP-12、MMP-13在结直肠癌组织中的表达率为43.6%,41.5%、83.5%和80.5%均高于在切缘正常肠黏膜组织中的表达率（4.2% 、5.5%、11.9%和13.1%）及在结直肠腺瘤组织中的表达率（24.2%、17.7%、69.4%和64.5%）（P均<0.05）。（2）CXCR5、CXCL13、MMP-12、MMP-13蛋白表达与淋巴结转移、远处转移、肿瘤分期及复发呈正相关(P<0.05)。CXCL13蛋白表达与组织分化程度呈正相关(P<0.05)。（3）CXCR5与CXCL13蛋白表达呈正相关(P<0.05)。CXCR5、CXCL13蛋白表达分别与MMP-12和MMP-13呈正相关(P<0.05)。结论 CXCR5、CXCL13、MMP-12、MMP-13的表达促进结直肠癌的发生、发展以及转移、复发, 可作为预测结直肠癌转移和复发的有价值指标。     

趋化因子CXCL12及其受体在人前列腺癌嗜神经过程中表达及相关机制

目的:阐述CXCL12-CXCR4在前列腺癌嗜神经过程中的作用及相关机制.方法:H＆E染色观察前列腺癌细胞对肿瘤组织及其周围神经的浸润.免疫组织化学方法检测CXCL12和CXCR4、MMP-2、MMP-9在22例人前列腺癌和20例前列腺增生组织中的表达差别,浸润神经的肿瘤细胞CXCR4和CXCL12的表达.结果:在人前列腺癌组织中,存在着较明显的肿瘤细胞侵犯神经现象,人前列腺癌组织中CXCL12、CXCR4、MMP-2和MMP-9表达阳性率均较前列腺增生组织明显升高(P<0.05),侵犯神经的肿瘤细胞表达CXCR4,神经组织内神经鞘膜细胞表达CXCL12.结论:在前列腺癌组织中存在肿瘤细胞嗜神经现象,肿瘤肿瘤细胞分泌CXCL12,CXCR4与MMP-2、MMP-9促进了癌细胞的嗜神经浸润.     

Mechanistic analysis of the antitumor efficacy of human natural killer cells against breast cancer cells

We investigated the role of human natural killer (NK) cells in the peripheral blood (PB) and liver in controlling breast cancer. The proportion of NK cells among liver mononuclear cells was significantly higher than among PB mononuclear cells. Liver NK cells inductively expressed higher levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) than PB NK cells in response to interleukin-2 (IL-2). Liver NK cells displayed higher cytotoxicity against various breast cancer cell lines (MDA-MB231, MDA-MB453, MDA-MB468, and MCF-7) after IL-2 stimulation than did PB NK cells. Anti-HER2 monoclonal antibody (mAb) promoted the cytotoxicity of both the types of NK cells toward HER2-expressing cell lines. All breast cancer cell lines highly expressed death-inducing TRAIL receptors, death receptor 4, but did not express death-inhibitory receptors (DcR1 and DcR2). Both PB and liver NK cell-induced cytotoxicity was inhibited partially by anti-TRAIL mAb and more profoundly by the combination of anti-TRAIL mAb and concanamycin A, indicating that TRAIL and perforin are involved. IL-2-stimulated liver and PB NK cells exhibited upregulated expression of CXCR3, which bind to the chemokines CXCL9, CXCL10, and CXCL11 secreted by breast cancer cells. We also found that IFN-γ promoted the production of CXCL10 from breast cancer cells. The results of this study show that IFN-γ secreted from NK cells likely promotes the production of CXCL10 from breast cancer cells, which in turn accelerates the migration of CXCR3-expressing NK cells into the tumor site. These findings suggest the possibility of a therapeutic approach by either activation of endogenous PB and liver NK cells or adoptive transfer of in vitro-activated autologous NK cells.     

Anti-proliferation Effects of Interferon-gamma on Gastric Cancer Cells

IFN-γ plays an indirect anti-cancer role through the immune system but may have direct negative effects oncancer cells. It regulates the viability of gastric cancer cells, so we examined whether it affects their proliferationand how that might be brought about. We exposed AGS, HGC-27 and GES-1 gastric cancer cell lines to IFN-γand found significantly reduced colony formation ability. Flow cytometry revealed no effect of IFN-γ on apoptosisof cell lines and no effect on cell aging as assessed by β-gal staining. Microarray assay revealed that IFN-γchanged the mRNA expression of genes related to the cell cycle and cell proliferation and migration, as well aschemokines and chemokine receptors, and immunity-related genes. Finally, flow cytometry revealed that IFN-γarrested the cells in the G1/S phase. IFN-γ may slow proliferation of some gastric cancer cells by affecting thecell cycle to play a negative role in the development of gastric cancer.     

Expression and Clinical Significance of REGy in Gastric Cancer Tissue and Variously Differentiated Gastric Cancer Cell Lines

OBJECTIVE To evaluate the REGy expression in gastric cancer tissue and gastric cancer cell lines of various differentiation levels and its clinical significance.METHODS Immunohistochemistry was used to detect the expression of REGy protein in 70 specimens of gastric cancer and 30 specimens of normal gastric mucosa. The relationship between the expression of REGy protein and the biological behaviors of gastric cancer was analyzed. RT-PCR and Western blot were used to detect the mRNA level and the protein expression of REGγ in normal gastric cell line GES-1, well differentiated gastric cancer cell line MKN-28, moderately differentiated gastric cancer cell line SGC-7901 and poorly differentiated gastric cancer cell line BGC-823.RESULTS The expression rate of REGγprotein in gastric cancer tissue (52/70, 74.29%) was significantly higher than that in normal gastric tissue (12/30, 40%) (P<0.01). The expression rate of REGywas correlated with tumor size (P<0.01), lymph node metastasis (P<0.05), differentiation degree (P<0.01), infiltration depth (P<0.01)and distant metastasis (P<0.05). RT-PCR analysis showed that theexpression of REGγ mRNA was 0.459±0.079 in the normal gastric mucosa cell line, 0.588±0.118 in the well differentiated gastric cancer cell line, 0.715±0.066 in the moderately differentiated gastric cancer cell line, and 0.873±0.099 in the poorly differentiated gastric cancer cell line, showing a negative correla- tion between REGγmRNA expression and differentiation level (P <0.05). Western blot analysis showed that the expression of REGy protein was 0.712±0.065 in the normal gastric mucosa cell line, 1.176±0.185 in the well differentiated gastric cancer cell line, 1.533 ±0.127 in the moderately differentiated gastric cancer cell line, and 2.061±0.398 in the poorly differentiated gastric cancer cell line, showing a negative correlation between REGγprotein expression and differentiation level (P<0.05).CONCLUSION REGγ is expressed in gastric cancer tissue and normal gastric tissue. In gastric cancer tissues, REGγexpression is positively correlated with the tumor size, lymph node metastasis,differentiation degree, infiltration depth and distant metastasis. Detecting the expression of REGy mRNA and protein is helpful for early diagnosis and predicting prognosis of gastric cancer.     

IFN-γ通过下调CXCL8抑制食管鳞状细胞癌的增殖和迁移

目的 研究干扰素-γ(IFN-γ)对食管鳞状细胞癌细胞株Eca9706增殖及迁移能力的影响,并初步探讨其作用机制.方法 体外进行细胞培养,用干扰素-γ作用细胞,镜下观察细胞形态变化,CCK-8实验检测细胞增殖能力,划痕实验和Transwell实验检测细胞迁移能力.采用Quantitative Real-time PCR...     

EBV-positive pyothorax-associated lymphoma expresses CXCL9 and CXCL10 chemokines that attract cytotoxic lymphocytes via CXCR3

Epstein–Barr virus (EBV)-positive diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) develops in the setting of long-standing inflammation. This type of lymphoma may have specific expression profiles of chemokines involved in the pathogenesis of DLBCL-CI. EBV-positive pyothorax-associated lymphoma (PAL) is a prototype of DLBCL-CI and represents a valuable model for the study of this disease category. Using a panel of PAL cell lines, we found that PAL cells expressed and secreted C–X–C motif chemokine ligands 9 and 10 (CXCL9 and CXCL10), the ligands of CXCR3, in contrast to EBV-negative DLBCL cell lines, which did not. Culture supernatants from PAL cell lines attracted CXCR3-expressing CD4⁺ T cells, CD8⁺ T cells, and CD56⁺ natural killer cells from human peripheral blood mononuclear cells. PAL cells injected into mice also attracted CXCR3-positive cytotoxic lymphocytes that expressed interferon-γ. The expression of CXCL9 and CXCL10 was detected in PAL tumor biopsy samples from patients, and CXCR3-positive lymphocytes were abundant in the tissue samples. Collectively, these findings suggest that CXCL9 and CXCL10 are produced by PAL cells and can elicit cytotoxic responses via CXCR3. This chemokine system is also likely to contribute to tissue necrosis, which is a signature histological feature of DLBCL-CI. Further studies are warranted to determine whether the CXCL9–CXCL10/CXCR3 axis exerts antitumor effects in DLBCL-CI.     

Programmed death (PD)-1/PD-ligand 1 blockade mediates antiangiogenic effects by tumor-derived CXCL10/11 as a potential predictive biomarker

Immune checkpoint inhibitor (ICI) programmed death (PD)-1/PD-ligand 1 (PD-L1) blockade has been approved for various cancers. However, the underlying antitumor mechanisms mediated by ICIs and the predictive biomarkers remain unclear. We report the effects of anti-PD-L1/PD-1 Ab in tumor angiogenesis. In syngeneic mouse models, anti-PD-L1 Ab inhibited tumor angiogenesis and induces net-like hypoxia only in ICI-sensitive cell lines. In tumor tissue and serum of ICI-sensitive cell line-bearing mice, interferon-γ (IFN-γ) inducible angiostatic chemokines CXCL10/11 were upregulated by PD-L1 blockade. In vitro, CXCL10/11 gene upregulation by IFN-γ stimulation in tumor cell lines correlated with the sensitivity of PD-L1 blockade. The CXCL10/11 receptor CXCR3-neutralizing Ab or CXCL11 silencing in tumor cells inhibited the antiangiogenic effect of PD-L1 blockade in vivo. In pretreatment serum of lung carcinoma patients receiving anti-PD-1 Ab, the concentration of CXCL10/11 significantly correlated with the clinical outcome. Our results indicate the antiangiogenic function of PD-1/PD-L1 blockade and identify tumor-derived CXCL10/11 as a potential circulating biomarker of therapeutic sensitivity.     

Modulation of CXCR3 ligand secretion by prostaglandin E2 and cyclooxygenase inhibitors in human breast cancer

Introduction

In murine breast cancer models, the two interferon-gamma (IFN-γ) inducible chemokines and CXC-chemokine receptor 3 (CXCR3) receptor ligands, monokine induced by γ-interferon (CXCL9) and interferon-γ-inducible protein-10 (CXCL10) impair tumor growth and metastasis formation through recruitment of natural killer (NK) cells and tumor-suppressive T lymphocytes. In human breast cancer, CXCL9 mRNA overexpression correlates with the number of tumor infiltrating lymphocytes and predicts response to different chemotherapeutic regimens. Raising the intratumoral CXCR3 ligand concentration is therefore a possible way to enhance immune intervention in breast cancer. Little is known, however, about expression levels and regulation of these chemokines in human breast cancer. Since the inhibition of cyclooxygenases (COX) has been shown to reduce tumor growth and incidence of metastases in a lymphocytic and IFN-γ dependent manner, we argued that COX isoenzymes are a pharmacologic target to increase intratumoral CXCR3 ligand concentration in human breast cancer.

Methods

CXCL9 was visualized in breast cancer specimens by immunohistochemistry, expression levels of CXCL9 and cyclooxygenases were determined by ELISA and western blotting, respectively. For regulation studies, Michigan Cancer Foundation-7 (MCF-7) and M.D. Anderson - Metastatic Breast 231 (MDA-MB 231) breast cancer cells were stimulated with IFN-γ with or without prostaglandin E₂ (PGE₂) or COX inhibitors (indomethacin, acetylsalicylic acid (ASA), celecoxib). CXCR3 ligand release from cells was measured by ELISA.

Results

Within the tumor microenvironment, cancer cells are the major source of CXCL9. PGE₂ impairs IFN-γ mediated CXCL9 and CXCL10 release from MCF-7 and MDA-MB 231 cells, and inhibition of endogenous cyclooxygenases by indomethacin or ASA correspondingly increases this secretion. Otherwise, high concentrations of the Cyclooxygenase-2 (COX-2) specific antagonist celecoxib have opposite effects and impair CXCL9 and CXCL10 release. In human breast cancer tissue specimens there is an inverse correlation between COX-2 overexpression and CXCL9 concentration, suggesting that the observed in vitro effects are of importance in vivo as well.

Conclusions

Suppressing endogenous PGE₂ synthesis by cyclooxygenase inhibition increases CXCL9 and CXCL10 release from breast cancer cells and is therefore a pharmacologic candidate to enhance intratumoral immune infiltration. Yet, to this end the unselective COX inhibitors ASA and indomethacin seem preferable to celecoxib that at higher concentrations reduces CXCR3 ligand release most probably due to COX independent mechanisms.     

Overexpression of CXCL1 and its receptor CXCR2 promote tumor invasion in gastric cancer

BackgroundThe chemokine (C-X-C motif) ligand 1 (CXCL1) and its receptor CXCR2 are associated with metastasis potential. Our studies were designed to clarify the CXCL1 and CXCR2 expression patterns and to explore their potential role in gastric cancerDesignThe expression of CXCL1 was determined in primary gastric cancer specimens using quantitative PCR, immunohistochemistry, and western blotting. To investigate the functional significance of CXCL1 expression, a CXCL1 expression vector and short hairpin RNA targeting the CXCL1 or CXCR2 were transfected into gastric cancer cell lines to examine the biological outcomes of these cells.ResultsThe expression of CXCL1 and CXCR2 was higher in gastric cancer tissues compared with adjacent noncancerous tissues. The upregulation of CXCL1 correlated significantly with tumor progression, advanced stage of gastric cancer patients, and was one of the independent prognostic factors for patient's survival. Furthermore, cancer cells expressing CXCL1 stably exhibited an increase in their migration and invasion ability, whereas CXCL1 or CXCR2 depletion significantly reduced the migration and invasion ability of each cell line.ConclusionsThese results provide strong evidence that CXCL1 plays an important role in gastric cancer progression and migration and suggest that CXCL1 is a promising marker for the detection and prognosis of gastric cancer.