Bile Acid and Inflammation Activate Gastric Cardia Stem Cells in a Mouse Model of Barrett-Like Metaplasia

被引：418

作者：

Quante, Michael ^{[1
,2
,11
]}

Bhagat, Govind ^{[2
,3
]}

Abrams, Julian A. ^{[1
,2
]}

Marache, Frederic ^{[1
,2
]}

Good, Pamela ^{[1
,2
]}

Lee, Michele D. ^{[1
,2
]}

Lee, Yoomi ^{[4
]}

Friedman, Richard ^{[5
]}

Asfaha, Samuel ^{[1
,2
]}

Dubeykovskaya, Zinaida ^{[1
,2
]}

Mahmood, Umar ^{[7
]}

Figueiredo, Jose-Luiz ^{[8
,9
]}

Kitajewski, Jan ^{[2
,6
]}

Shawber, Carrie ^{[2
,6
]}

Lightdale, Charles J. ^{[1
,2
]}

Rustgi, Anil K. ^{[10
]}

Wang, Timothy C. ^{[1
,2
]}

机构：

[1] Columbia Univ, Dept Med, Med Ctr, Div Digest & Liver Dis, New York, NY 10032 USA

[2] Columbia Univ, Dept Med, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA

[3] Columbia Univ, Dept Med, Dept Pathol & Cell Biol, New York, NY 10032 USA

[4] Columbia Univ, Dept Med, Med Ctr, Div Hematol & Oncol, New York, NY 10032 USA

[5] Columbia Univ, Dept Biomed Informat, Med Ctr, New York, NY 10032 USA

[6] Columbia Univ, Dept Pathol Obstet & Gynecol, Med Ctr, New York, NY 10032 USA

[7] Harvard Univ, Sch Med, Nucl Med & Mol Imaging, Boston, MA 02114 USA

[8] Harvard Univ, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA

[9] Massachusetts Gen Hosp, Boston, MA 02114 USA

[10] Univ Penn, Div Gastroenterol, Dept Med & Genet, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[11] Tech Univ Munich, Med Klin, Klinikum Rechts Isar, D-81675 Munich, Germany

来源：

CANCER CELL | 2012年 / 21卷 / 01期

关键词：

DYSPLASIA-ADENOCARCINOMA SEQUENCE; INTESTINAL METAPLASIA; SQUAMOUS EPITHELIUM; OXIDATIVE STRESS; REFLUX DISEASE; DNA-DAMAGE; ESOPHAGUS; EXPRESSION; CANCER; PROGRESSION;

D O I：

10.1016/j.ccr.2011.12.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Esophageal adenocarcinoma (EAC) arises from Barrett esophagus (BE), intestinal-like columnar metaplasia linked to reflux esophagitis. In a transgenic mouse model of BE, esophageal overexpression of interleukin-1 beta phenocopies human pathology with evolution of esophagitis, Barrett-like metaplasia and EAC. Histopathology and gene signatures closely resembled human BE, with upregulation of TFF2, Bmp4, Cdx2, Notch1, and IL-6. The development of BE and EAC was accelerated by exposure to bile acids and/or nitrosamines, and inhibited by IL-6 deficiency. Lgr5(+) gastric cardia stem cells present in BE were able to lineage trace the early BE lesion. Our data suggest that BE and EAC arise from gastric progenitors due to a tumor-promoting IL-1 beta-IL-6 signaling cascade and DII1-dependent Notch signaling.

引用

页码：36 / 51

页数：16

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