杜渐,
宋英茜,
刘一平,
罗海峰,
谭广^,
大连医科大学附属第一医院 肝胆外科, 辽宁 大连 116011

基金项目: 辽宁省自然科学基金指导计划项目（20170540266）


详细信息 作者简介: 杜渐(1981-), 男, 副主任医师。E-mail:dujian1030@163.com





通讯作者: 谭广, 教授。E-mail:tanguang009@sina.com 中图分类号: R735.9


摘要:目的探讨胰腺癌微环境下趋化因子C-X-C配体5（CXCL5）的表达及其与患者不良预后的关系。方法应用免疫组化检测38例胰腺癌组织标本中CXCL5的表达；应用ELISA检测正常胰腺导管上皮细胞系HPDE6-C7及胰腺癌细胞系AsPC-1，PANC-1，BxPC-3上清液中CXCL5的表达；分析CXCL5表达与胰腺癌患者临床病理资料及总生存率的相关性；采用BxPC-3细胞上清液（BxCM）体外模拟胰腺癌微环境，流式细胞仪、ELISA及细胞毒性T淋巴细胞（CTL）杀伤实验评价肿瘤微环境下CXCL5对树突状细胞（DC）免疫功能的影响。结果CXCL5在胰腺癌组织中表达量显著高于对应癌旁组织（4.448 vs. 1.910，P < 0.05），在各胰腺癌细胞系上清液中表达量也均明显高于HPDE6-C7细胞（均P < 0.05）；CXCL5表达量与胰腺癌的TNM分期、血管侵犯有关（均P < 0.05）；CXCL5高表达胰腺癌患者的总生存率明显低于低表达者（5.263% vs. 26.316%，P < 0.05）；下调CXCL5能够显著降低BxCM对DC的抑制（均P < 0.05）。结论CXCL5在胰腺癌中表达异常增高且与胰腺癌的TNM分期及不良预后密切相关，其机制可能与抑制DC的免疫功能有关。
关键词: 胰腺肿瘤/
CXCL5/
树突状细胞/
肿瘤微环境


Abstract:ObjectiveTo investigate the expression of CXCL5 in pancreatic cancer microenvironment and its association with poor prognosis of the patients.MethodsThe expression of CXCL5 in 38 human pancreatic cancer tissues was detected by immunohistochemistry. Meanwhile, the CXCL5 expression levels in the conditioned mediums of normal pancreatic duct epithelial cell line HPDE6-C7 and pancreatic cancer cell lines AsPC-1, PANC-1 and BxPC-3 were determined by ELISA. The relations of CXCL5 expression with clinicopathologic parameters and overall survival rate of pancreatic cancer patients were analyzed. In addition, BxPC-3 cell conditioned medium (BxCM) was used to mimic tumor microenvironment. The immunologic functions of DCs inhibited by CXCL5 were detected by flowcytometry, ELISA and cytotoxic lymphocytes reaction (CTL).ResultsIn tumor tissues compared with their adjacent non-tumor tissues, the expression of CXCL5 was significantly increased (4.448 vs. 1.910, P < 0.05), and the CXCL5 expression levels in all pancreatic carcinoma cell lines were notably higher than that in HPDE6-C7 cells (all P < 0.05). Meanwhile, the expression of CXCL5 was closely associated with the TNM stage and vascular invasion of pancreatic cancer(P < 0.05). The postoperative overall survival rate was decreased in patients with high CXCL5 expression compared with those with low expression (5.263% vs. 26.316%, P < 0.05). The immunologic functions of DC were significantly inhibited by BxCM (all P < 0.05), and these inhibitory effects could be markedly rescued through down-regulation of CXCL5 (all P < 0.05).ConclusionThe aberrantly up-regulated expression of CXCL5 in pancreatic cancer tissue is closely related with malignancy and poor prognosis. The mechanisms may be associated with its inhibition on the immunologic functions of DC.
Keywords:pancreatic tumor/
CXCL5/
dendritic cell/
tumor microenvironment

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