The Intestinal Stem Cell Signature Identifies Colorectal Cancer Stem Cells and Predicts Disease Relapse

被引：760

作者：

Merlos-Suarez, Anna ^{[1
]}

Barriga, Francisco M. ^{[1
]}

Jung, Peter ^{[1
]}

Iglesias, Mar ^{[3
]}

Virtudes Cespedes, Maria ^{[4
,5
]}

Rossell, David ^{[2
]}

Sevillano, Marta ^{[1
]}

Hernando-Momblona, Xavier ^{[1
]}

da Silva-Diz, Victoria ^{[6
]}

Munoz, Purificacion ^{[6
]}

Clevers, Hans ^{[7
,8
]}

Sancho, Elena ^{[1
]}

Mangues, Ramon ^{[4
,5
]}

Batlle, Eduard ^{[1
,9
]}

机构：

[1] IRB, Oncol Program, Barcelona 08028, Spain

[2] IRB, Biostat Unit, Barcelona 08028, Spain

[3] Univ Autonoma Barcelona, Hosp Univ Mar, Dept Pathol, Barcelona 08003, Spain

[4] MICINN, CIBER BBN, Inst Biomed Res IIB St Pau, Barcelona 08025, Spain

[5] MICINN, CIBER BBN, Networking Res Ctr Bioengn Biomat & Nanomed, Barcelona 08025, Spain

[6] Bellvitge Biomed Res Inst IDIBELL, Catalan Canc Epigenet & Biol Program PEBC, Barcelona 08907, Spain

[7] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands

[8] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands

[9] ICREA, Barcelona, Spain

来源：

CELL STEM CELL | 2011年 / 8卷 / 05期

关键词：

COLON-CANCER; EMBRYONIC STEM; BETA-CATENIN; IN-VITRO; EXPRESSION; PROGRESSION; DIFFERENTIATION; TARGET; TUMORS; DEATH;

D O I：

10.1016/j.stem.2011.02.020

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

A frequent complication in colorectal cancer (CRC) is regeneration of the tumor after therapy. Here, we report that a gene signature specific for adult intestinal stem cells (ISCs) predicts disease relapse in CRC patients. ISCs are marked by high expression of the EphB2 receptor, which becomes gradually silenced as cells differentiate. Using EphB2 and the ISC marker Lgr5, we have FACS-purified and profiled mouse ISCs, crypt proliferative progenitors, and late transient amplifying cells to define a gene program specific for normal ISCs. Furthermore, we discovered that ISC-specific genes identify a stem-like cell population positioned at the bottom of tumor structures reminiscent of crypts. EphB2 sorted ISC-like tumor cells display robust tumor-initiating capacity in immunodeficient mice as well as long-term self-renewal potential. Taken together, our data suggest that the ISC program defines a cancer stem cell niche within colorectal tumors and plays a central role in CRC relapse.

引用

页码：511 / 524

页数：14

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