Down-regulation of integrin αvβ3 expression and integrin-mediated signaling in glioma cells by adenovirus-mediated transfer of antisense urokinase-type plasminogen activator receptor (uPAR) and sense p16 genes (Retracted article. See vol. 295, pg. 13134, 2020)
Down-regulation of integrin αvβ3 expression and integrin-mediated signaling in glioma cells by adenovirus-mediated transfer of antisense urokinase-type plasminogen activator receptor (uPAR) and sense p16 genes (Retracted article. See vol. 295, pg. 13134, 2020)
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DOI：
10.1074/jbc.m104334200
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发表时间：
2001-12-14
影响因子：
4.8
通讯作者：
Rao, JS
中科院分区：
文献类型：
--
作者：
Adachi, Y;Lakka, SS;Rao, JS
细胞外基质和细胞表面整合素受体之间的相互作用不仅导致细胞粘附，还导致影响细胞迁移、增殖和存活的细胞内信号事件。玻璃体连接蛋白受体α (v) β(3)整合素在胶质瘤细胞生物学中具有重要意义。尿激酶型纤溶酶原激活物受体（uPAR）的表达最近被证明与α (v) β(3)整合素的表达共同调节。此外，神经胶质瘤细胞中p16蛋白的恢复抑制了α (v) β(3)整合素介导的这些细胞在玻璃体连接蛋白上的扩散。因此，我们假设腺病毒介导的uPAR下调和p16的过表达可能下调了胶质瘤细胞中α (v) β(3)整合素的表达和整合素介导的信号传导，从而打败了恶性phe。notype。在这项研究中，我们使用了复制缺陷腺病毒载体，其中包含一个uPAR反义表达盒（Ad-uPAR）或野生型p16 cDNA (Ad-p16)，以及一个双链腺病毒构建体，其中uPAR反义和p16义表达盒（Ad-uPAR/p16）都插入到载体的el缺失区域。在玻璃体连接蛋白存在的情况下，用Ad-uPAR、Ad-p16或Ad-uPAR/p16感染恶性胶质瘤细胞系SNB19可导致α (v) β(3)整合素表达降低和整合素介导的生物学效应，包括粘附、迁移、增殖和存活。我们的研究结果支持同时靶向uPAR和p16治疗胶质瘤的治疗潜力。
Interaction between the extracellular matrix and integrin receptors on cell surfaces leads not only to cell adhesion but also to intracellular signaling events that affect cell migration, proliferation, and survival. The vitronectin receptor alpha (v)beta (3) integrin is of key importance in glioma cell biology. The expression of urokinase-type plasminogen activator receptor (uPAR) was recently shown to co-regulate with the expression of alpha (v)beta (3), integrin. Moreover, restoration of the p16 protein in glioma cells inhibits the alpha (v)beta (3) integrin-mediated spreading of those cells on vitronectin. Thus we hypothesized that adenovirus-mediated down-regulation of uPAR and overexpression of p16 might down-regulate the expression of alpha (v)beta (3) integrin and the integrin-mediated signaling in glioma cells, thereby defeating the malignant phe. notype. In this study, we used replication-deficient adenovirus vectors that contain either a uPAR antisense expression cassette (Ad-uPAR) or wild-type p16 cDNA (Ad-p16) and a bicistronic adenovirus construct in which both the uPAR antisense and p16 sense expression cassettes (Ad-uPAR/p16) are inserted in the El-deleted region of the vector. Infecting the malignant glioma cell line SNB19 with Ad-uPAR, Ad-p16, or Ad-uPAR/p16 in the presence of vitronectin resulted in decreased alpha (v)beta (3) integrin expression and integrin-mediated biological effects, including adhesion, migration, proliferation, and survival Our results support the therapeutic potential of simultaneously targeting uPAR and p16 in the treatment of gliomas.