Downregulation of junctional adhesion molecule-A is involved in the progression of clear cell renal cell carcinoma
Downregulation of junctional adhesion molecule-A is involved in the progression of clear cell renal cell carcinoma
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DOI：
10.1016/j.bbrc.2009.01.100
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发表时间：
2009-03-06
影响因子：
3.1
通讯作者：
Pfeilschifter, Josef
中科院分区：
文献类型：
--
作者：
Gutwein, Paul;Schramme, Anja;Pfeilschifter, Josef
连接粘附分子-A (JAM-A) 是紧密连接的组成部分之一，参与细胞旁通透性、细胞极性、粘附、迁移和血管生成等重要过程。在这里，我们描述了健康人肾脏的远曲小管、连接小管和集合管细胞中 JAM-A 的表达。此外，JAM-A在近曲小管细胞中微弱表达。使用免疫荧光、FACS 和蛋白质印迹分析，我们在体外研究了肾小管细胞中的 JAM-A 表达。有趣的是，用 IFN-γ 和 TNF-α 处理 HK-2 细胞导致金属蛋白酶介导的 JAM-A 下调。重要的是，在组织微阵列中，透明细胞肾细胞癌患者的 JAM-A 蛋白表达显着下调。此外，用JAM-A特异性siRNA敲低JAM-A可诱导RCC4细胞的迁移。总之，JAM-A 的下调是肾癌发展的早期事件，并增加肾癌细胞的迁移。 (C) 2009 Elsevier Inc. 保留所有权利。
Junctional adhesion molecule-A (JAM-A) is one component of tight junctions which are involved in important processes like paracellular permeability, cell polarity, adhesion, migration and angiogenesis,. Here we describe JAM-A expression in distal convoluted tubule, connecting tubule, and in cells of the collecting duct of the healthy human kidney. In addition, JAM-A was weakly expressed in cells of the proximal tubule. Using immunofluorescence, FACS and Western blot analysis we investigated JAM-A expression in tubular cells in vitro. Interestingly, treatment of HK-2 cells with IFN-gamma and TNF-alpha resulted in a metalloproteinase mediated downregulation of JAM-A. Importantly, in a tissue micro-array JAM-A protein expression was significantly downregulated in patients with clear cell renal cell carcinoma. Furthermore, knockdown of JAM-A with JAM-A specific siRNA induced the migration of RCC4 cells. In summary, downregulation of JAM-A is an early event in the development of renal cancer and increases the migration of renal cancer cells. (C) 2009 Elsevier Inc. All rights reserved.