Li Yang, Liu Wei, Fang Li, Nan Juan, Zhang Zhanque, Zhou Qinghua
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical Univercity General Hospital, Tianjin 300052, China.
Zhongguo Fei Ai Za Zhi. 2010 Nov;13(11):1016-20. doi: 10.3779/j.issn.1009-3419.2010.11.04.
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.
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.
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 (P > 0.05). 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 (P < 0.05).
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.
已证实C-C趋化因子受体7（CCR7）与非小细胞肺癌（NSCLC）的淋巴结转移密切相关，但NSCLC转移的机制尚不完全清楚。本研究旨在探讨CCR7和基质金属蛋白酶-9（MMP-9）在NSCLC中的表达及其表达关系，并探讨CCR7促进NSCLC转移的机制。
采用免疫组织化学SP法检测90例人原发性NSCLC标本中CCR7和MMP-9蛋白的表达。人肺大细胞系BE1细胞用CCL19预孵育24小时；采用逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测MMP-9的变化。
免疫组织化学显示，CCR7分布于肿瘤细胞的细胞质和/或细胞膜，MMP-9分布于癌细胞的细胞质。NSCLC中CCR7和MMP-9蛋白的表达分别为70%（63/90）和65.5%（59/90）。CCR7和MMP-9蛋白的表达与NSCLC的临床分期（P=0.003，P=0.001）和淋巴结转移（P=0.004，P=0.003）密切相关，但与年龄、性别、组织学类型无关（P>0.05）。此外，CCR7与MMP-9之间存在显著相关性（r=0.342，P=0.001）。另外，CCL19预孵育组MMP-9 mRNA和蛋白水平升高（P<0.05）。
CCR7和MMP-9的表达与NSCLC的侵袭和转移显著相关。在NSCLC中，MMP-9的上调受CCR7调控。
