TY - JOUR
T1 - The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse
AU - Merlos-Suárez, Anna
AU - Barriga, Francisco M.
AU - Jung, Peter
AU - Iglesias, Mar
AU - Céspedes, María Virtudes
AU - Rossell, David
AU - Sevillano, Marta
AU - Hernando-Momblona, Xavier
AU - Da Silva-Diz, Victoria
AU - Muñoz, Purificación
AU - Clevers, Hans
AU - Sancho, Elena
AU - Mangues, Ramón
AU - Batlle, Eduard
N1 - Funding Information:
We thank Genentech, Inc. for providing anti-EphB2 antibody Mab 2H9, Evarist Planet (IRB, Barcelona) for assistance with statistical methods, H.G. Palmer (Vall d'Hebron Hospital) for support, M. Trias (Hospital de la Santa Creu i Sant Pau) for tumor samples, A. Calon for assistance with bioinformatics, IRB Functional Genomics Facility (IRB) for technical assistance in microarray hybridization experiments, A. Rodolosse for help with ISHs, J. Comas and R. Álvarez (UB, Barcelona) for expert technical assistance with the FACS, I. Joval for figure artwork, C. Nadal and X. Garcia (Clinic Hospital, Barcelona) for help with samples and discussions, and to all members of the Batlle Lab for support. A.M.-S. holds an AECC postdoctoral fellowship, and F.M.B. holds an IRB/La Caixa PhD fellowship. This work has been supported by grants to E.B. from ERC (FP7-EU) and MICINN (Plan Nacional I+D+i and Consolider programs) and by grants PS09/00965 (MICINN) and NanoCoMets (CIBER-BBN) to R.M.
PY - 2011/5/6
Y1 - 2011/5/6
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.
UR - https://www.scopus.com/pages/publications/79955681163
U2 - 10.1016/j.stem.2011.02.020
DO - 10.1016/j.stem.2011.02.020
M3 - Article
C2 - 21419747
AN - SCOPUS:79955681163
SN - 1934-5909
VL - 8
SP - 511
EP - 524
JO - Cell stem cell
JF - Cell stem cell
IS - 5
ER -