Drug Discovery II, DSP Cancer Institute, Dainippon Sumitomo Pharma Co., Ltd, Osaka, Japan.
Cancer Sci. 2014 May;105(5):560-7. doi: 10.1111/cas.12394. Epub 2014 Apr 19.
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.
靶向肿瘤血管生成是癌症治疗的一种既定策略。由于血管生成不仅限于癌症等病理状况，因此需要能够区分生理和病理血管生成的分子标志物，以开发更有效和更安全的癌症治疗方法。为了鉴定这些分子，我们使用 DNA 微阵列分析，随后使用定量逆转录聚合酶链反应分析，确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 中差异上调的基因。使用 siRNA 介导的基因沉默进行的功能分析揭示了五个涉及 mTEC 增殖或迁移的新的肿瘤内皮细胞标志物。在人肾细胞癌标本的肿瘤血管中，DEF6 和 TMEM176B 的表达上调，表明它们可能是肾细胞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，并鉴定了可能用于针对癌症治疗中的肿瘤血管生成的新的肿瘤内皮细胞标志物。
