Suppression of MMP-9 activity by NDRG2 expression inhibits clear cell renal cell carcinoma invasion
Suppression of MMP-9 activity by NDRG2 expression inhibits clear cell renal cell carcinoma invasion
复制标题
NDRG2 表达抑制 MMP-9 活性可抑制透明细胞肾细胞癌侵袭
DOI：
10.1007/s12032-012-0265-1
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发表时间：
2012-12-01
期刊：
影响因子：
3.4
通讯作者：
Bao, Ting-Yi
中科院分区：
文献类型：
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作者：
Ma, Jian-Jun;Kong, Ling-Min;Bao, Ting-Yi
NDRG（N-Myc downstream-regulated）基因家族的成员已被证明在人类恶性肿瘤中发挥多种作用。最近的研究表明NDRG 2在肾透明细胞癌（CCRCC）中的表达降低，并抑制细胞增殖，但NDRG 2在CCRCC侵袭中的作用尚未被描述。我们检测了NDRG 2蛋白在CCRCC样本中的表达以及NDRG 2表达与CCRCC患者生存率之间的关系。采用实时荧光定量RT-PCR和免疫组化方法检测60例癌旁组织及癌旁正常组织中NDRG 2的表达。通过腺病毒或siRNA上调或下调NDRG 2来检测细胞侵袭的变化。我们发现NDRG 2在CCRCC中的表达在mRNA和蛋白水平上显著下调，并且与肿瘤的侵袭性行为如TNM分期（P= 0.003）、Fuhrman分级（P= 0.024）、肿瘤侵袭（P= 0.001）和肿瘤复发（P= 0.004）以及较短的患者生存率（P= 0.0041）负相关。NDRG 2还可通过调节MMP-9的表达和活性来抑制CCRCC细胞的侵袭。因此，NDRG 2可以抑制肿瘤细胞基于细胞外基质的侵袭，从而在抑制CCRCC肿瘤转移中发挥重要作用。NDRG 2表达也可能是CCRCC的一个重要预后指标。
Members of the NDRG (N-Myc downstream-regulated) gene family have been shown to play a variety of roles in human malignancies. Recently, it was shown decreased expression in clear cell renal cell carcinoma (CCRCC) and inhibited cell proliferation, but the role of the NDRG2 in CCRCC invasion has not been described. We examined the expression of NDRG2 protein in CCRCC samples and the association between NDRG2 expression and CCRCC patients survival. Real-time RT-PCR and immunohistochemical analysis were used to measure NDRG2 expression in 60 paired CCRCC and adjacent normal tissues. Changes in cell invasion were detected by up- or down-regulating NDRG2 by adenovirus or siRNA. We found that NDRG2 expression is significantly down-regulated in CCRCC at mRNA and protein levels in a manner negatively associated with aggressive tumor behaviors, such as TNM stage (P= 0.003), Fuhrman’s grade (P= 0.024), tumor invasion (P= 0.001) and tumor recurrence (P= 0.004), as well as shorter patient survival rates (P= 0.0041). Furthermore, NDRG2 could suppress CCRCC cell invasion through regulating MMP-9 expression and activity. So, these results suggest that NDRG2 can inhibit extracellular matrix-based tumor cell invasion and thereby play important roles in suppressing tumor metastasis in CCRCC. NDRG2 expression may also be a significant prognostic indicator for CCRCC.