E1A expression might becontrol led by miR- 214incells with low adenovirus productivity
E1A expression might becontrol led by miR- 214incells with low adenovirus productivity
复制标题
腺病毒生产力低的细胞中E1A表达可能由miR-214控制
DOI：
10.1016/j.virusres.2012.09.001
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
他4名
中科院分区：
文献类型：
--
作者：
Yanagawa-Matsuda A;KitamuraT;他4名
肿瘤血管生成是实体瘤进展和转移所必需的。环氧合酶（考克斯）-2在肿瘤生长和侵袭中起重要作用，它激活控制细胞增殖、迁移、凋亡和血管生成的信号通路。据报道，考克斯-2在许多癌细胞中表达。几项研究报道了用考克斯-2抑制剂（考克斯-2 is）成功治疗癌细胞。然而，考克斯-2抑制对肿瘤内皮的影响仍有待阐明。我们的研究表明，考克斯-2在手术切除的人类肿瘤血管中表达。为了研究体外抑制考克斯-2对肿瘤内皮细胞的影响，我们从小鼠的人黑素瘤和口腔癌异种移植物中分离肿瘤内皮细胞（TEC），其中我们证实通过用考克斯-2 is NS 398抑制血管生成来抑制肿瘤生长。与正常内皮细胞（NEC）相比，TEC中的考克斯-2 mRNA上调。NS 398在TEC中抑制细胞迁移和增殖，但在NEC中不抑制。NS 398在体内的作用与体外结果一致。考克斯-2抑制剂显著抑制了循环中CD 133 +/血管内皮生长因子受体-2+细胞的数量。此外，在考克斯-2 i治疗后，肿瘤血管中祖细胞标志物阳性细胞的数量减少，这表明祖细胞向肿瘤中的归巢也被阻断。我们得出结论，NS 398特异性靶向TEC和血管祖细胞，而不影响NEC。
Tumor angiogenesis is necessary for solid tumor progression and metastasis. Cyclooxygenase (COX)‐2 is known to play an important role in cancer growth and invasion, and it activates the signaling pathways controlling cell proliferation, migration, apoptosis, and angiogenesis. COX‐2 is reported to be expressed in many cancer cells. Several studies have reported successful treatment of cancer cells with COX‐2 inhibitors (COX‐2is). However, the effect of COX‐2 inhibition on the tumor endothelium remains to be elucidated. Our study shows that COX‐2 is expressed in the vasculature of surgically resected human tumors. To investigate the effects of COX‐2 inhibition on the tumor endotheliumin vitro, we isolated tumor endothelial cells (TECs) from human melanoma and oral carcinoma xenografts in mice, in which we confirmed that tumor growth was suppressed by inhibiting angiogenesis with the COX‐2is NS398. COX‐2 mRNA was upregulated in TECs compared to normal endothelial cells (NECs). Cell migration and proliferation were suppressed by NS398 in TECs but not in NECs. The effects of NS398in vivowere consistent with thein vitroresults. The number of CD133+/vascular endothelial growth factor receptor‐2+cells in circulation was significantly suppressed by COX‐2 inhibition. In addition, the number of progenitor marker‐positive cells decreased in the tumor blood vessels after COX‐2i treatment, which suggests that the homing of progenitor cells into the tumor was also blocked. We conclude that NS398 specifically targets both TECs and vascular progenitor cells without affecting NECs.