title: The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse.
abstract: 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.
authors.affiliation: Oncology Program, Institute for Research in Biomedicine (IRB), Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Merlos-Suárez
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Barriga
authors.forename: Peter
authors.initials: P
authors.lastname: Jung
authors.forename: Mar
authors.initials: M
authors.lastname: Iglesias
authors.forename: María Virtudes
authors.initials: MV
authors.lastname: Céspedes
authors.forename: David
authors.initials: D
authors.lastname: Rossell
authors.forename: Marta
authors.initials: M
authors.lastname: Sevillano
authors.forename: Xavier
authors.initials: X
authors.lastname: Hernando-Momblona
authors.forename: Victoria
authors.initials: V
authors.lastname: da Silva-Diz
authors.forename: Purificación
authors.initials: P
authors.lastname: Muñoz
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.forename: Elena
authors.initials: E
authors.lastname: Sancho
authors.forename: Ramón
authors.initials: R
authors.lastname: Mangues
authors.forename: Eduard
authors.initials: E
authors.lastname: Batlle
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation; D002469:Cell Separation; D022081:Cell Surface Extensions / Q000473:pathology; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007422:Intestines / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D036223:Receptor, EphB3 / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D055153:Stem Cell Niche
chemical_list: C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled; D036223:Receptor, EphB3