DNA Damage in CD133-Positive Cells in Barrett’s Esophagus and Esophageal Adenocarcinoma

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 p...

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Main Authors: Raynoo Thanan, Ning Ma, Yusuke Hiraku, Katsunori Iijima, Tomoyuki Koike, Tooru Shimosegawa, Mariko Murata, Shosuke Kawanishi
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2016/7937814
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author Raynoo Thanan
Ning Ma
Yusuke Hiraku
Katsunori Iijima
Tomoyuki Koike
Tooru Shimosegawa
Mariko Murata
Shosuke Kawanishi
author_facet Raynoo Thanan
Ning Ma
Yusuke Hiraku
Katsunori Iijima
Tomoyuki Koike
Tooru Shimosegawa
Mariko Murata
Shosuke Kawanishi
author_sort Raynoo Thanan
collection DOAJ
description 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.
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spelling doaj-art-3dbd0816e3b24c00a959456784d5935d2025-08-20T03:55:40ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/79378147937814DNA Damage in CD133-Positive Cells in Barrett’s Esophagus and Esophageal AdenocarcinomaRaynoo Thanan0Ning Ma1Yusuke Hiraku2Katsunori Iijima3Tomoyuki Koike4Tooru Shimosegawa5Mariko Murata6Shosuke Kawanishi7Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandFaculty of Nursing Science, Suzuka University of Medical Science, Suzuka, Mie 513-8670, JapanDepartment of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanDivision of Gastroenterology, Tohoku University Hospital, Sendai 980-8574, JapanDivision of Gastroenterology, Tohoku University Hospital, Sendai 980-8574, JapanDivision of Gastroenterology, Tohoku University Hospital, Sendai 980-8574, JapanDepartment of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanFaculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670, JapanBarrett’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.http://dx.doi.org/10.1155/2016/7937814
spellingShingle Raynoo Thanan
Ning Ma
Yusuke Hiraku
Katsunori Iijima
Tomoyuki Koike
Tooru Shimosegawa
Mariko Murata
Shosuke Kawanishi
DNA Damage in CD133-Positive Cells in Barrett’s Esophagus and Esophageal Adenocarcinoma
Mediators of Inflammation
title DNA Damage in CD133-Positive Cells in Barrett’s Esophagus and Esophageal Adenocarcinoma
title_full DNA Damage in CD133-Positive Cells in Barrett’s Esophagus and Esophageal Adenocarcinoma
title_fullStr DNA Damage in CD133-Positive Cells in Barrett’s Esophagus and Esophageal Adenocarcinoma
title_full_unstemmed DNA Damage in CD133-Positive Cells in Barrett’s Esophagus and Esophageal Adenocarcinoma
title_short DNA Damage in CD133-Positive Cells in Barrett’s Esophagus and Esophageal Adenocarcinoma
title_sort dna damage in cd133 positive cells in barrett s esophagus and esophageal adenocarcinoma
url http://dx.doi.org/10.1155/2016/7937814
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