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

Anna Merlos-Suárez, Francisco M. Barriga, Peter Jung, Mar Iglesias, María Virtudes Céspedes, David Rossell, Marta Sevillano, Xavier Hernando-Momblona, Victoria Da Silva-Diz, Purificación Muñoz, Hans Clevers, Elena Sancho, Ramón Mangues, Eduard Batlle

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

735 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)511-524
Aantal pagina's14
TijdschriftCell Stem Cell
Volume8
Nummer van het tijdschrift5
DOI's
StatusGepubliceerd - 6 mei 2011
Extern gepubliceerdJa

Vingerafdruk

Duik in de onderzoeksthema's van 'The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse'. Samen vormen ze een unieke vingerafdruk.

Citeer dit