The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse

TY - JOUR

T1 - The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse

AU - Merlos-Suarez, A.

AU - Barriga, F.M.

AU - Jung, P.

AU - Iglesias, M.

AU - Cespedes, M.V.

AU - Rossell, D.

AU - Sevillano, M.

AU - Hernando-Momblona, X.

AU - da Silva-Diz, V.

AU - Munoz, P.

AU - Clevers, H.

AU - Sancho, E.

AU - Mangues, R.

AU - Batlle, E.

N1 - Reporting year: 2011

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.1016/j.stem.2011.02.020

DO - 10.1016/j.stem.2011.02.020

M3 - Article

SN - 1934-5909

VL - 8

SP - 511

EP - 524

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 5

ER -