DNA Damage in CD133-Positive Cells in Barrett's Esophagus and Esophageal Adenocarcinoma.
DNA Damage in CD133-Positive Cells in Barrett's Esophagus and Esophageal Adenocarcinoma.
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DOI：
10.1155/2016/7937814
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发表时间：
2016
影响因子：
4.6
通讯作者：
Kawanishi S
中科院分区：
文献类型：
--
作者：
Thanan R;Ma N;Hiraku Y;Iijima K;Koike T;Shimosegawa T;Murata M;Kawanishi S
由胃食管反流引起的巴雷特食管（BE）是巴雷特食管腺癌（BEA）（一种与炎症相关的癌症）的主要危险因素。慢性炎症和随后的组织损伤可能会在富含活性氧/氮的环境下激活祖细胞。我们之前报道了在BE组织的柱状上皮细胞和BEA组织的癌细胞中氧化/硝化应激介导的诱变DNA损伤、8-oxo-7,8-二氢-2'-脱氧鸟苷（8-oxodG）和8-硝基鸟嘌呤的形成。我们研究了 BEA 发育与氧化/硝化 DNA 损伤和干细胞假说相关的机制。我们通过免疫组织化学分析检测了 BE 和 BEA 患者活检标本中 8-硝基鸟嘌呤和 8-oxodG 的形成以及干细胞标记物 (CD133) 的表达，并与正常受试者进行比较。 CD133在BE和BEA组织的柱状上皮细胞顶面以及BEA组织中癌细胞的细胞质和细胞膜中检测到。 DNA 损伤和 CD133 共定位于柱状上皮细胞和癌细胞中。它们在这些组织中的相对染色强度显着高于正常受试者。我们的结果表明，顶端表面表达CD133的BE柱状上皮细胞经历炎症介导的DNA损伤，并且突变细胞获得了细胞质CD133表达的癌症干细胞的特性。
Barrett's esophagus (BE) caused by gastroesophageal reflux is a major risk factor of Barrett's esophageal adenocarcinoma (BEA), an inflammation-related cancer. Chronic inflammation and following tissue damage may activate progenitor cells under reactive oxygen/nitrogen species-rich environment. We previously reported the formation of oxidative/nitrative stress-mediated mutagenic DNA lesions, 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-nitroguanine, in columnar epithelial cells of BE tissues and cancer cells of BEA tissues. We investigated the mechanisms of BEA development in relation to oxidative/nitrative DNA damage and stem cell hypothesis. We examined 8-nitroguanine and 8-oxodG formation and the expression of stem cell marker (CD133) in biopsy specimens of patients with BE and BEA by immunohistochemical analysis in comparison with those of normal subjects. CD133 was detected at apical surface of columnar epithelial cells of BE and BEA tissues, and the cytoplasm and cell membrane of cancer cells in BEA tissues. DNA lesions and CD133 were colocalized in columnar epithelial cells and cancer cells. Their relative staining intensities in these tissues were significantly higher than those in normal subjects. Our results suggest that BE columnar epithelial cells with CD133 expression in apical surface undergo inflammation-mediated DNA damage, and mutated cells acquire the property of cancer stem cells with cytoplasmic CD133 expression.