Editors' ChoiceStem Cells

A Fountain of Cancer

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Science Translational Medicine  04 May 2011:
Vol. 3, Issue 81, pp. 81ec64
DOI: 10.1126/scitranslmed.3002570

Astronaut Sally Ride described the experience of preparing to launch into space as “sitting on a big explosion waiting to happen.” Colorectal cancer patients can relate; after surgery and chemotherapy, cancer can recur in up to 40% of patients. Unfortunately, physicians remain unable to predict who will fall in this unlucky group, making the wait difficult to bear. Now, Merlos-Suárez et al. may have identified the cellular source of colorectal cancer relapse, paving the way for the development of better prognostic tools.

In normal colon tissue, intestinal stem cells (ISCs) that reside at the base of mucosal wells, named crypts, expand through mitosis and move upward toward the crypt tip. The cells then undergo cell cycle arrest and terminal differentiation, finally becoming the mucosal epithelium of the colon. In the recent study, the investigators identified in mouse ISCs a gene signature that was specifically marked by high expression of the ephrin type-B receptor 2 gene(Ephb2), which encodes a receptor tyrosine kinase, the leucine-rich repeat–containing G protein–coupled receptor 5 gene (Lgr5), which encodes a G-coupled protein receptor of unknown function, and ~50 other genes. This gene signature also defined a specific population of stem-like cells at the base of colorectal tumor structures in mice that were morphologically similar to normal mouse intestinal crypts. The authors then similarly inspected tumor samples from 340 colorectal patients and discovered a 10-fold increase in the relative risk of recurrence in patients whose tumors displayed high expression of the human counterparts of the mouse ISC genes, relative to patients whose tumors showed low expression of these genes.

To test whether the mouse colorectal tumor cells with the ISC gene signature were cancer stem cells, the investigators isolated the cells and introduced them into an immunodeficient mouse model. The stem-like cancer cells demonstrated both a tumor-initiating capacity and self-renewal capability in vivo. These findings pinpoint potential markers that may allow a clinician to predict a patient’s future with respect to recurrence. These differentially expressed genes also may give rise to therapeutic targets that quell cancer stem cells.

A. Merlos-Suárez et al., The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell Stem Cell 17 March 2011 (10.1016/j.stem.2011.02.020). [PubMed]

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