Format

Send to

Choose Destination
Cell Stem Cell. 2015 Jun 4;16(6):627-38. doi: 10.1016/j.stem.2015.04.013.

Krt19(+)/Lgr5(-) Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine.

Author information

1
Division of Digestive and Liver Diseases, Department of Medicine, Irving Cancer Research Center, Columbia University, New York, NY 10032, USA; Department of Medicine, University of Western Ontario, London, ON N6A 5W9, Canada.
2
Division of Digestive and Liver Diseases, Department of Medicine, Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
3
Centre for Tumour Biology, Barts Cancer Institute, London EC1M 6BQ, UK.
4
II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
5
Department of Genetics and Development, Columbia University, New York, NY 10032, USA.
6
Department of Radiation Oncology, Albert Einstein College of Medicine, New York, NY 10467, USA.
7
Division of Gastroenterology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
8
Division of Digestive and Liver Diseases, Department of Medicine, Irving Cancer Research Center, Columbia University, New York, NY 10032, USA. Electronic address: tcw21@columbia.edu.

Abstract

Epithelium of the colon and intestine are renewed every 3 days. In the intestine there are at least two principal stem cell pools. The first contains rapid cycling crypt-based columnar (CBC) Lgr5(+) cells, and the second is composed of slower cycling Bmi1-expressing cells at the +4 position above the crypt base. In the colon, however, the identification of Lgr5(-) stem cell pools has proven more challenging. Here, we demonstrate that the intermediate filament keratin-19 (Krt19) marks long-lived, radiation-resistant cells above the crypt base that generate Lgr5(+) CBCs in the colon and intestine. In colorectal cancer models, Krt19(+) cancer-initiating cells are also radioresistant, while Lgr5(+) stem cells are radiosensitive. Moreover, Lgr5(+) stem cells are dispensable in both the normal and neoplastic colonic epithelium, as ablation of Lgr5(+) stem cells results in their regeneration from Krt19-expressing cells. Thus, Krt19(+) stem cells are a discrete target relevant for cancer therapy.

PMID:
26046762
PMCID:
PMC4457942
DOI:
10.1016/j.stem.2015.04.013
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center