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

Merlos-Suárez, Anna; Barriga de Vicente, Francisco Martín, 1983-; Jung, Peter; Iglesias Coma, Mar; Céspedes, María Virtudes; Rossell, David; Sevillano, Marta; Hernando-Momblona, Xavier; Silva-Diz, Victoria da; Muñoz, Purificación; Clevers, Hans; Sancho, Elena; Mangues, Ramon; Batlle Gómez, Eduard

doi:http://dx.doi.org/10.1016/j.stem.2011.02.020

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

Citation

Merlos-Suárez A, Barriga FM, Jung P, Iglesias M, Céspedes MV, Rossell D et al. The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell Stem Cell. 2011 May 6;8(5):511-24. DOI: 10.1016/j.stem.2011.02.020

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.