Cancer Cell：肿瘤相关血管中高度表达的13种基因

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Cancer Cell：肿瘤相关血管中高度表达的13种基因


  生物谷报道：美国国家癌症研究所（National Cancer Institute，NCI）研究人员最近在小鼠和人类实验中发现一组特定在肿瘤相关血管中高度表达的基因。这些基因及其编码的蛋白，是选择性切断肿瘤血供而不伤及健康组织血管的潜在药物靶标，克服了靶向血管生长的现代抗癌策略的一个主要问题。详细研究过程刊登于6月Cancer Cell杂志。

  血管生长过程又名血管新生（angiogenesis），肌体中普遍存在，对器官的生长和修复非常重要。在许多疾病包括大部分癌症中，这种被精细调节的过程失衡，正常血的管生长改道向患病组织输送营养和氧气。以癌症为例，血管新生使癌细胞逃逸、迁移到肌体其它部位。研究人员试图通过鉴别刺激血管的分子、发展阻断这些分子作用的药物来抑制疾病相关的血管新生。然而，阻断血管新生需要肿瘤和正常细胞之间的平衡，许多相关分子对正常的血管生长（如月经、怀孕或组织修复时）也非常关键，以这些分子为靶标的药物在健康组织也会引发副作用。

  Brad St. Croix博士与其同事选择小鼠肝脏来源的血管内皮细胞，因为肝脏再生时可被诱导出新的血管。通过对比再生肝脏细胞和肝癌细胞的基因表达图谱，研究人员发现13种基因在疾病相关血管新生过程种过量表达，其中一种名为CD276的基因，编码的蛋白定位于细胞表面。

  为了确定这些在小鼠研究中取得的发现在人类癌症中也成立，研究人员检测CD276在癌症患者来源的内皮细胞中的表达情况，结果在结肠癌、肺癌、乳腺癌、食道癌和膀胱癌的肿瘤相关血管细胞中发现CD276过量表达，而且这些蛋白在肿瘤细胞本身也过量表达，说明合适的抑制分子能够实现一箭双雕的效果——攻克肿瘤细胞自身和喂养肿瘤细胞的血管。

  St. Croix说，鉴于CD275在多种人类肿瘤血管中过量表达，CD276可能是新一代选择性作用于疾病相关血管的药物的靶标。

原始出处:

Cancer Cell, Vol 11, 539-554, 12 June 2007

Article

Genes that Distinguish Physiological and Pathological Angiogenesis
Steven Seaman,1 Janine Stevens,1 Mi Young Yang,1 Daniel Logsdon,2 Cari Graff-Cherry,2 and Brad St. Croix1,

1 Tumor Angiogenesis Section, Mouse Cancer Genetics Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA
2 Basic Research Program, SAIC, National Cancer Institute at Frederick, Frederick, MD 21702, USA


Corresponding author
Brad St. Croix
stcroix@ncifcrf.gov

Summary

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.