Identification of novel targets for antiangiogenic therapy by comparing the gene expressions of tumor and normal endothelial cells.
Identification of novel targets for antiangiogenic therapy by comparing the gene expressions of tumor and normal endothelial cells.
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DOI：
10.1111/cas.12394
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发表时间：
2014-05
期刊：
影响因子：
5.7
通讯作者：
Hida K
中科院分区：
文献类型：
--
作者：
Otsubo T;Hida Y;Ohga N;Sato H;Kai T;Matsuki Y;Takasu H;Akiyama K;Maishi N;Kawamoto T;Shinohara N;Nonomura K;Hida K
靶向肿瘤血管生成是癌症治疗的既定策略。由于血管生成并不局限于癌症等病理条件，因此需要能够区分生理性和病理性血管生成的分子标记物来开发更有效和更安全的癌症治疗方法。为了鉴定这些分子，我们利用DNA微阵列分析和定量逆转录聚合酶链式反应分析，测定了小鼠肿瘤内皮细胞(MTEC)和小鼠正常内皮细胞的基因表达谱。我们鉴定了131个在mTEC中差异表达的基因。利用siRNA介导的基因沉默进行功能分析，发现了5个与mTEC增殖或迁移有关的新的肿瘤内皮细胞标志物。DEF6和TMEM176B在人肾细胞癌标本的肿瘤血管中表达上调，提示它们是肾癌抗血管生成干预的潜在靶点。比较基因表达分析揭示了肿瘤内皮细胞和正常内皮细胞之间的分子差异，并发现了新的肿瘤内皮细胞标记物，可能被用来靶向肿瘤血管生成用于癌症治疗。
Targeting tumor angiogenesis is an established strategy for cancer therapy. Because angiogenesis is not limited to pathological conditions such as cancer, molecular markers that can distinguish between physiological and pathological angiogenesis are required to develop more effective and safer approaches for cancer treatment. To identify such molecules, we determined the gene expression profiles of murine tumor endothelial cells (mTEC) and murine normal endothelial cells using DNA microarray analysis followed by quantitative reverse transcription–polymerase chain reaction analysis. We identified 131 genes that were differentially upregulated in mTEC. Functional analysis using siRNA-mediated gene silencing revealed five novel tumor endothelial cell markers that were involved in the proliferation or migration of mTEC. The expression of DEF6 and TMEM176B was upregulated in tumor vessels of human renal cell carcinoma specimens, suggesting that they are potential targets for antiangiogenic intervention for renal cell carcinoma. Comparative gene expression analysis revealed molecular differences between tumor endothelial cells and normal endothelial cells and identified novel tumor endothelial cell markers that may be exploited to target tumor angiogenesis for cancer treatment.
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DOI：
10.1165/ajrcmb.20.2.3368
发表时间：
1999-02-01
影响因子：
6.4
作者：
Lurton, J;Rose, TM;Narayanan, AS
通讯作者：
Narayanan, AS
影响因子：
3.4
作者：
Hurwitz, Herbert
通讯作者：
Hurwitz, Herbert
影响因子：
8
作者：
Banyard, J;Anand-Apte, B;Zetter, BR
通讯作者：
Zetter, BR
影响因子：
11.2
作者：
Hida, K;Hida, Y;Klagsbrun, M
通讯作者：
Klagsbrun, M
影响因子：
8.8
作者：
Kamba, T;McDonald, D M
通讯作者：
McDonald, D M