Krt19+/Lgr5- Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine

被引：178

作者：

Asfaha, Samuel ^{[1
,7
]}

Hayakawa, Yoku ^{[1
]}

Muley, Ashlesha ^{[1
]}

Stokes, Sarah ^{[1
]}

Graham, Trevor A. ^{[3
]}

Ericksen, Russell E. ^{[1
]}

Westphalen, Christoph B. ^{[1
]}

von Burstin, Johannes ^{[5
]}

Mastracci, Teresa L. ^{[4
]}

Worthley, Daniel L. ^{[1
]}

Guha, Chandhan ^{[6
]}

Quante, Michael ^{[5
]}

Rustgi, Anil K. ^{[2
]}

Wang, Timothy C. ^{[1
]}

机构：

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

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

[3] Barts Canc Inst, Ctr Tumour Biol, London EC1M 6BQ, England

[4] Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA

[5] Tech Univ Munich, Klinikum Rechts Isar, Med Klin 2, D-81675 Munich, Germany

[6] Albert Einstein Coll Med, Dept Radiat Oncol, New York, NY 10467 USA

[7] Univ Western Ontario, Dept Med, London, ON N6A 5W9, Canada

来源：

CELL STEM CELL | 2015年 / 16卷 / 06期

关键词：

EXPRESSION MARKS; IN-VITRO; LGR5; IDENTIFICATION; POPULATIONS; ORIGIN; CRYPTS; TUMORS; BMI1; MICE;

D O I：

10.1016/j.stem.2015.04.013

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Epithelium of the colon and intestine are renewed every 3 days. In the intestine there are at least two principal stem cell pools. The first contains rapid cycling crypt-based columnar (CBC) Lgr5(+) cells, and the second is composed of slower cycling Bmi1-expressing cells at the +4 position above the crypt base. In the colon, however, the identification of Lgr5(-) stem cell pools has proven more challenging. Here, we demonstrate that the intermediate filament keratin-19 (Krt19) marks long-lived, radiation-resistant cells above the crypt base that generate Lgr5(+) CBCs in the colon and intestine. In colorectal cancer models, Krt19(+) cancer-initiating cells are also radioresistant, while Lgr5(+) stem cells are radiosensitive. Moreover, Lgr5(+) stem cells are dispensable in both the normal and neoplastic colonic epithelium, as ablation of Lgr5(+) stem cells results in their regeneration from Krt19-expressing cells. Thus, Krt19(+) stem cells are a discrete target relevant for cancer therapy.

引用

页码：627 / 638

页数：12

共 30 条

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Identification of stem cells in small intestine and colon by marker gene Lgr5 [J].