Neuronal pentraxin 2 supports clear cell renal cell carcinoma by activating the AMPA-selective glutamate receptor-4.
Neuronal pentraxin 2 supports clear cell renal cell carcinoma by activating the AMPA-selective glutamate receptor-4.
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DOI：
10.1158/0008-5472.can-14-0210
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发表时间：
2014-09-01
期刊：
影响因子：
11.2
通讯作者：
Copland JA
中科院分区：
文献类型：
--
作者：
von Roemeling CA;Radisky DC;Marlow LA;Cooper SJ;Grebe SK;Anastasiadis PZ;Tun HW;Copland JA
透明细胞肾细胞癌（ccRCC）是肾癌最常见的亚型，并且具有最高的转移性疾病倾向。最近对ccRCC基因特征的描述揭示了与肿瘤细胞迁移和侵袭相关的几个因素；然而，导致恶性肿瘤的具体事件并没有很好地定义。此外，对于转移性疾病患者，仍然缺乏能够产生长期、可持续反应的靶向治疗。我们在这里发现神经元戊烷素2 （NPTX2）在ccRCC原发肿瘤和转移瘤中特异性过表达，并且它通过与α-氨基-3-羟基-5-甲基-4-异氧唑丙酸（AMPA）受体亚基GluR4的相互作用促进肿瘤细胞活力和细胞迁移。我们提出NPTX2作为一种新的分子靶点，用于治疗被诊断为转移性疾病或有转移性疾病风险的ccRCC患者。
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, and has the highest propensity to manifest as metastatic disease. Recent characterizations of the genetic signature of ccRCC have revealed several factors correlated with tumor cell migration and invasion; however the specific events driving malignancy are not well defined. Furthermore, there remains a lack of targeted therapies that result in long-term, sustainable response in patients with metastatic disease. We show here that neuronal pentraxin 2 (NPTX2) is over-expressed specifically in ccRCC primary tumors and metastases, and that it contributes to tumor cell viability and promotes cell migration through its interaction with the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR4. We propose NPTX2 as a novel molecular target for therapy for ccRCC patients diagnosed with or at risk of developing metastatic disease.