Identification of novel vascular targets in lung cancer.
Identification of novel vascular targets in lung cancer.
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DOI：
10.1038/bjc.2014.626
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发表时间：
2015-02-03
影响因子：
8.8
通讯作者：
Bicknell, R.
中科院分区：
文献类型：
--
作者：
Zhuang, X.;Herbert, J. M. J.;Lodhia, P.;Bradford, J.;Turner, A. M.;Newby, P. M.;Thickett, D.;Naidu, U.;Blakey, D.;Barry, S.;Cross, D. A. E.;Bicknell, R.
肺癌仍然是癌症相关死亡的主要原因，这主要是由于缺乏有效的治疗方法。肿瘤血管靶向策略提供了一个有吸引力的替代方案；然而，肺癌血管系统的分子特征还没有得到很好的研究。这项工作旨在确定肺癌中新的肿瘤血管靶点。采用酶消化新鲜组织，Ulex凝集素包裹磁珠捕获内皮细胞的方法分离肺癌新鲜肿瘤标本中的内皮细胞。从健康和肿瘤肺组织分离的内皮细胞利用微阵列技术进行了全人类基因组表达谱分析。生物信息学分析证实肿瘤内皮细胞表达血管生成因子、基质金属蛋白酶和细胞表面跨膜蛋白。通过RNA-SEQ、实时定量聚合酶链式反应分析和免疫组织化学方法对预测的肿瘤血管新靶点进行了验证。STEAP1在82名肺癌患者上的进一步详细表达谱证实了STEAP1是肿瘤血管系统中的一个新靶点。使用siRNA沉默对STEAP1进行的功能分析表明，STEAP1在内皮细胞迁移和管状形成中发挥作用。肺内肿瘤细胞表面内皮细胞标志物的鉴定对治疗性抗体和疫苗的研制具有重要意义。
Lung cancer remains the leading cause of cancer-related death, largely owing to the lack of effective treatments. A tumour vascular targeting strategy presents an attractive alternative; however, the molecular signature of the vasculature in lung cancer is poorly explored. This work aimed to identify novel tumour vascular targets in lung cancer. Enzymatic digestion of fresh tissue followed by endothelial capture with Ulex lectin-coated magnetic beads was used to isolate the endothelium from fresh tumour specimens of lung cancer patients. Endothelial isolates from the healthy and tumour lung tissue were subjected to whole human genome expression profiling using microarray technology. Bioinformatics analysis identified tumour endothelial expression of angiogenic factors, matrix metalloproteases and cell-surface transmembrane proteins. Predicted novel tumour vascular targets were verified by RNA-seq, quantitative real-time PCR analysis and immunohistochemistry. Further detailed expression profiling of STEAP1 on 82 lung cancer patients confirmed STEAP1 as a novel target in the tumour vasculature. Functional analysis of STEAP1 using siRNA silencing implicates a role in endothelial cell migration and tube formation. The identification of cell-surface tumour endothelial markers in lung is of interest in therapeutic antibody and vaccine development.
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影响因子：
45.3
作者：
Huang, Yen-Tsung;Heist, Rebecca S.;Christiani, David C.
通讯作者：
Christiani, David C.
DOI：
10.1073/pnas.96.25.14523
发表时间：
1999-12-07
影响因子：
11.1
作者：
Hubert, RS;Vivanco, I;Afar, DEH
通讯作者：
Afar, DEH
影响因子：
4
作者：
Dicke, Nikolai;Pielensticker, Nicole;Willecke, Klaus
通讯作者：
Willecke, Klaus
影响因子：
168.9
作者：
Goldstraw, Peter;Ball, David;Shepherd, Frances A.
通讯作者：
Shepherd, Frances A.
影响因子：
11.2
作者：
Garcia-Hernandez, Maria de la Luz;Gray, Andrew;Kast, W. Martin
通讯作者：
Kast, W. Martin