Tumor-associated endothelial cells display GSTP1 and RARβ2 promoter methylation in human prostate cancer
Tumor-associated endothelial cells display GSTP1 and RARβ2 promoter methylation in human prostate cancer
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DOI：
10.1186/1479-5876-4-13
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发表时间：
2006-03-02
影响因子：
7.4
通讯作者：
Libutti, SK
中科院分区：
文献类型：
--
作者：
Grover, AC;Tangrea, MA;Libutti, SK
背景：正常的血液供应对肿瘤的生长和增殖至关重要。然而，血管向肿瘤募集的机制仍然知之甚少。理想情况下，对血管细胞进行彻底的分子评估将是我们理解这一过程的关键。然而，迄今为止，对肿瘤相关血管内皮细胞的分子组成知之甚少，部分原因是很难从异质组织环境中分离出纯粹的内皮细胞群。方法：在这里，我们描述了一种最新发展的技术，表达显微解剖，从肿瘤微环境中分离内皮细胞。通过QMS-PCR方法评估解剖样本中GSTP1和RAR β 2启动子的甲基化状态。结果：比较GSTP1和RAR β 2启动子甲基化数据，我们发现在肿瘤区域，上皮和内皮中分别检测到100%和88%的甲基化。在非肿瘤组织区域几乎没有甲基化。结论：我们应用了精确的显微解剖技术从组织中分离内皮细胞，使DNA分析如启动子甲基化状态成为可能。观察结果表明，表观遗传改变可能在决定肿瘤相关脉管系统的表型中起作用。
Background: A functional blood supply is essential for tumor growth and proliferation. However, the mechanism of blood vessel recruitment to the tumor is still poorly understood. Ideally, a thorough molecular assessment of blood vessel cells would be critical in our comprehension of this process. Yet, to date, there is little known about the molecular makeup of the endothelial cells of tumor-associated blood vessels, due in part to the difficulty of isolating a pure population of endothelial cells from the heterogeneous tissue environment.Methods: Here we describe the use of a recently developed technique, Expression Microdissection, to isolate endothelial cells from the tumor microenvironment. The methylation status of the dissected samples was evaluated for GSTP1 and RAR beta 2 promoters via the QMS-PCR method.Results: Comparing GSTP1 and RAR beta 2 promoter methylation data, we show that 100% and 88% methylation is detected, respectively, in the tumor areas, both in epithelium and endothelium. Little to no methylation is observed in non-tumor tissue areas.Conclusion: We applied an accurate microdissection technique to isolate endothelial cells from tissues, enabling DNA analysis such as promoter methylation status. The observations suggest that epigenetic alterations may play a role in determining the phenotype of tumor-associated vasculature.