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CCR7上调MMP-9表达促进非小细胞肺癌转移

ISSN号：1009-3419
期刊名称：《中国肺癌杂志》
时间：0
分类：R734.2[医药卫生—肿瘤;医药卫生—临床医学]
作者机构：[1]天津医科大学总医院,天津市肺癌研究所,天津市肺癌转移与肿瘤做环境实验室,天津300052, [2]天津药物研究院,天津市新药设计与发现重点实验室,天津300191, [3]中国医科大学附属第一医院肝胆外科,沈阳110001, [4]山西省芮城县人民医院,芮城044600
相关基金：国家自然科学基金重点项目（No.30430300）; 国家“973”项目（No.2010CB529405）; 天津市科技创新体系建设项目（No.07SYSYSF0500）;天津市科技支撑计划重点项目（No.06YFSZSF05300）

作者：李洋[1], 刘巍[2], 方莉[3], 南娟[1], 张占雀, 周清华[1]

关键词： CCR7, MMP-9, 肺肿瘤, 转移, CCR7, MMP-9, Lung neoplasms, Metastasis

中文摘要：

背景与目的趋化因子激素受体（CC chemokine receptor7,CCR7）与非小细胞肺癌（non-small celllung cancer,NSCLC）的淋巴结转移密切相关,但CCR7促进其淋巴结转移的机制尚不明了。本研究通过观察CCR7和MMP-9在NSCLC组织中的表达和相互关系,探讨CCR7促进NSCLC淋巴结转移的机制。方法应用免疫组织化学染色（SP法）检测90例NSCLC组织中CCR7、MMP-9的表达;将BE1细胞经趋化因子CCL19处理24h后,应用RT-PCR和Western blot方法检测MMP-9mRNA和蛋白表达水平。结果免疫组织化学结果显示：CCR7主要表达于癌细胞胞质和（或）胞膜,MMP-9主要表达于癌细胞胞质,NSCLC中CCR7、MMP-9阳性表达率分别为70%（63/90）和65.5%（59/90）,χ2检验显示CCR7和MMP-9表达与NSCLC的临床病理分期（P=0.003,P=0.001）和淋巴结转移（P=0.004,P=0.003）密切相关,而与年龄、组织学类型、分化程度无关（P〉0.05）。此外,CCR7和MMP-9表达正相关（r=0.342,P=0.001）。CCL21处理组BE1细胞后MMP-9mRNA和蛋白水平均上调（P〈0.05）。结论 CCR7和MMP-9表达与NSCLC侵袭转移密切相关,CCL19/CCR7通过上调NSCLC中MMP-9表达促进其转移。

英文摘要：

Background and objective It has been proven that CC chemokine receptor 7 （CCR7） is closely related with the lymph node metastasis of non-small cell lung cancer （NSCLC）,but the mechanism of NSCLC metastasis is not very clear.The aim of this study is to investigate the expressions of CCR7 and MMP-9 in NSCLC and the relationship of their expressions,and to explore the mechanism of CCR7 promoting NSCLC metastasis.Methods The expressions of CCR7 and MMP-9 protein were detected in 90 specimens of human primary NSCLC by immunohistochemical SP method.Human large lung cell line BE1 cells were pre-incubated with CCL19 for 24 h;the changes of MMP-9 were detected by RT-PCR and Western blot.Results Immunohistochemistry showed that CCR7 was distributed in cytoplasm and/or membrane of tumor cells and MMP-9 was distributed in cytoplasm of cancer cells.The expressions of CCR7 and MMP-9 protein were found to be 70% （63/90） and 65.5% （59/90） in NSCLC,respectively.The expressions of CCR7 and MMP-9 protein were closely related to the clinical stages （P=0.003,P=0.001） and lymph node metastasis （P=0.004,P=0.003） of NSCLC,but there was no correlation with age,gender,histology （P0.05）.Furthermore,a significant correlation was found between CCR7 and MMP-9 （r=0.342,P=0.001）.In addition,the expressions of MMP-9 mRNA and protein levels were increased in CCL19 pre-incubated group （P0.05）.Conclusion The expressions of CCR7 and MMP-9 are significantly associated with NSCLC invasion and metastasis.The upregulation of MMP-9 is regulated by CCR7 in NSCLC.

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