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CCL19/CCR7对前列腺癌细胞增殖和迁移的影响。

The effect of CCL19/CCR7 on the proliferation and migration of cell in prostate cancer.

作者信息

Peng Cheng, Zhou Keliang, An Sensheng, Yang Jie

机构信息

Department of Urology, 456 Hospital of PLA, No. 25 Wuyingshan Road, Jinan, 250031, China.

出版信息

Tumour Biol. 2015 Jan;36(1):329-35. doi: 10.1007/s13277-014-2642-1. Epub 2014 Sep 26.

Abstract

Multiple studies have shown that CC motif chemokine ligand 19 (CCL19) promotes cell proliferation in several human cancers. In this study, we investigated the clinical significance of CCL19 and its specific receptor CCR7 and its function in our large collection of prostate samples. Between August 2000 and December 2013, 108 patients with histologically confirmed prostate cancer (PCa) and 80 with benign prostate hyperplasia (BPH) were recruited into the study. Quantitative RT-PCR immunohistochemistry analyses were used to quantify CCL19 and CCR7 expression in PCa cell lines and clinical samples. The functional role of CCL19 in PCa cell lines was evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and invasion. The positive rate of CCL19 staining was 87.04 % (94/108) in 108 cases of prostatic carcinoma and 16.25 % (13/80) in 80 cases of BPH, and high expression of CCR7 was observed in 83.33 % (90/108) of the PCa tissues versus (17.50 %; 14/80) of the BPH tissues, the difference of CCL19 and CCR7 expression between two groups was statistically significant, respectively. The results were confirmed by quantitative real-time PCR. CCL19 and CCR7 were significantly elevated in all five PCa cell lines when compared to the RWPE-1 cells. Silencing of CCL19 inhibited the proliferation of DU-145 cells which have a relatively high level of CCL19 in a time- and concentration-dependent manner, and the invasion and migration of DU-145 cells were distinctly suppressed. Our data suggest that the pathogenesis of human PCa maybe mediated by the CCL19/CCR7 axis, and CCL19 inhibition treatment may provide a promising strategy for the anti-tumor therapy of PCa.

摘要

多项研究表明,CC基序趋化因子配体19(CCL19)在多种人类癌症中促进细胞增殖。在本研究中,我们在大量前列腺样本中研究了CCL19及其特异性受体CCR7的临床意义及其功能。2000年8月至2013年12月,108例经组织学确诊的前列腺癌(PCa)患者和80例良性前列腺增生(BPH)患者被纳入研究。采用定量逆转录聚合酶链反应免疫组织化学分析方法对PCa细胞系和临床样本中CCL19和CCR7的表达进行定量。通过小干扰RNA介导的蛋白缺失,随后进行细胞增殖和侵袭分析,评估CCL19在PCa细胞系中的功能作用。108例前列腺癌患者中CCL19染色阳性率为87.04%(94/108),80例BPH患者中为16.25%(13/80),83.33%(90/108)的PCa组织中观察到CCR7高表达,而BPH组织中为17.50%(14/80),两组间CCL19和CCR7表达差异具有统计学意义。结果通过定量实时聚合酶链反应得到证实。与RWPE-1细胞相比,所有五种PCa细胞系中CCL19和CCR7均显著升高。CCL19沉默以时间和浓度依赖性方式抑制了CCL19水平相对较高的DU-145细胞的增殖,并且DU-145细胞的侵袭和迁移明显受到抑制。我们的数据表明,人类PCa的发病机制可能由CCL19/CCR7轴介导,CCL19抑制治疗可能为PCa的抗肿瘤治疗提供一种有前景的策略。

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