Seaman Steven, Stevens Janine, Yang Mi Young, Logsdon Daniel, Graff-Cherry Cari, St Croix Brad
Tumor Angiogenesis Section, Mouse Cancer Genetics Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Cancer Cell. 2007 Jun;11(6):539-54. doi: 10.1016/j.ccr.2007.04.017.
To unravel the normal vasculature transcriptome and determine how it is altered by neighboring malignant cells, we compared gene expression patterns of endothelial cells derived from the blood vessels of eight normal resting tissues, five tumors, and regenerating liver. Organ-specific endothelial genes were readily identified, including 27 from brain. We also identified 25 transcripts overexpressed in tumor versus normal endothelium, including 13 that were not found in the angiogenic endothelium of regenerating liver. Most of the shared angiogenesis genes have expected roles in cell-cycle control, but those specific for tumor endothelium were primarily cell surface molecules of uncertain function. These studies reveal striking differences between physiological and pathological angiogenesis potentially important for the development of tumor-specific, vascular-targeted therapies.
为了解析正常脉管系统转录组并确定其如何被邻近的恶性细胞改变,我们比较了源自八个正常静息组织、五个肿瘤和再生肝脏血管的内皮细胞的基因表达模式。很容易识别出器官特异性内皮基因,包括来自大脑的27个基因。我们还鉴定出25种在肿瘤内皮细胞中相对于正常内皮细胞过度表达的转录本,其中13种在再生肝脏的血管生成内皮细胞中未发现。大多数共享的血管生成基因在细胞周期控制中具有预期作用,但那些肿瘤内皮细胞特有的基因主要是功能不确定的细胞表面分子。这些研究揭示了生理和病理血管生成之间的显著差异,这可能对肿瘤特异性血管靶向治疗的发展具有重要意义。