PMID- 21419747 OWN - NLM STAT- MEDLINE DCOM- 20111003 LR - 20230108 IS - 1875-9777 (Electronic) IS - 1875-9777 (Linking) VI - 8 IP - 5 DP - 2011 May 6 TI - The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. PG - 511-24 LID - 10.1016/j.stem.2011.02.020 [doi] 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. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Merlos-Suarez, Anna AU - Merlos-Suarez A AD - Oncology Program, Institute for Research in Biomedicine (IRB), Baldiri Reixac 10, 08028 Barcelona, Spain. FAU - Barriga, Francisco M AU - Barriga FM FAU - Jung, Peter AU - Jung P FAU - Iglesias, Mar AU - Iglesias M FAU - Cespedes, Maria Virtudes AU - Cespedes MV FAU - Rossell, David AU - Rossell D FAU - Sevillano, Marta AU - Sevillano M FAU - Hernando-Momblona, Xavier AU - Hernando-Momblona X FAU - da Silva-Diz, Victoria AU - da Silva-Diz V FAU - Munoz, Purificacion AU - Munoz P FAU - Clevers, Hans AU - Clevers H FAU - Sancho, Elena AU - Sancho E FAU - Mangues, Ramon AU - Mangues R FAU - Batlle, Eduard AU - Batlle E LA - eng SI - GEO/GSE27605 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110317 PL - United States TA - Cell Stem Cell JT - Cell stem cell JID - 101311472 RN - 0 (LGR5 protein, human) RN - 0 (Receptors, G-Protein-Coupled) RN - EC 2.7.10.1 (Receptor, EphB3) SB - IM MH - Adult Stem Cells/*metabolism/pathology MH - Animals MH - Cell Differentiation MH - Cell Separation MH - Cell Surface Extensions/pathology MH - Cells, Cultured MH - Colonic Neoplasms/*diagnosis/pathology/physiopathology MH - Flow Cytometry MH - Gene Expression Profiling MH - Gene Expression Regulation, Developmental MH - Humans MH - Intestines/*pathology MH - Mice MH - Mice, Knockout MH - Neoplasm Recurrence, Local MH - Neoplastic Stem Cells/*metabolism/pathology MH - Prognosis MH - Receptor, EphB3/genetics/*metabolism MH - Receptors, G-Protein-Coupled/metabolism MH - Stem Cell Niche EDAT- 2011/03/23 06:00 MHDA- 2011/10/04 06:00 CRDT- 2011/03/23 06:00 PHST- 2010/04/26 00:00 [received] PHST- 2011/01/10 00:00 [revised] PHST- 2011/02/28 00:00 [accepted] PHST- 2011/03/23 06:00 [entrez] PHST- 2011/03/23 06:00 [pubmed] PHST- 2011/10/04 06:00 [medline] AID - S1934-5909(11)00110-X [pii] AID - 10.1016/j.stem.2011.02.020 [doi] PST - ppublish SO - Cell Stem Cell. 2011 May 6;8(5):511-24. doi: 10.1016/j.stem.2011.02.020. Epub 2011 Mar 17.