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Stem cells and their implications for colorectal cancer

Nature Reviews Gastroenterology & Hepatology volume 8, pages 90–100 (2011)Cite this article

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Abstract

The colonic crypt is home to several multipotent stem cells. These stem cells reside in a niche at the base of the crypt, which controls their behavior and maintains the stem cell's homeostasis through a variety of signaling pathways and interactions. Several attempts have been made to define markers that can identify colonic stem cells, the most useful of which is Lgr5, a Wnt target gene. Although the crypt base contains several stem cells, each colonic crypt comprises a single clone of cells. Investigators have attempted to reconcile these apparently contradictory observations by conducting research into stem cell division. The propagation of stem-cell-acquired mutations through a crypt results in a monocryptal adenoma that, through crypt fission, develops into a microadenoma. Some early adenomas become polyclonal through an as yet unknown mechanism. The discovery of subpopulations of cancer cells that can initiate tumors when implanted into mice has renewed interest in the existence of cancer stem cells, especially with regard to their implications for the use of chemotherapy. Various potential markers of cancer stem cells have been investigated, particularly CD133, but the cancer stem cell theory still has some limitations.

Key Points

  • Several stem cells are thought to reside at the base of each colonic crypt, in a niche that maintains their homeostatic environment and regulates their activities

  • Colonic stem cells can divide either symmetrically (resulting in two daughter or two stem cells) or asymmetrically (resulting in one daughter and one stem cell)

  • The progeny of one stem cell will come to dominate the niche (niche succession) and eventually the entire crypt (monoclonal conversion), facilitating the spread of mutations within a crypt

  • Oncogenic mutations spread through the colonic epithelium (field cancerization) via crypt fission, during which crypts divide laterally; interactions between adjacent crypts might explain why many adenomas are polyclonal

  • Established tumors are thought to contain cancer stem cells, which could be responsible for the continued growth, invasion and metastasis of the tumor

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Figure 1: The colonic stem cell and its niche.
Figure 2: Niche succession, monoclonal conversion and crypt fission.
Figure 3: Possible explanations for the polyclonality of colonic adenomas.

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  1. Centre for Digestive Diseases, Blizard Institute, Barts and The London School of Medicine and Dentistry, 4 Newark Street, London, E1 2AT, UK

    Sebastian S. Zeki

  2. Cancer Research UK London Research Institute—Lincoln's Inn Fields, 44 Lincoln's Inn Fields, London, WC2A 3LY, UK

    Trevor A. Graham & Nicholas A. Wright

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S. S. Zeki researched data for and wrote the article. T. A. Graham and N. A. Wright made substantial contributions to discussions of the article content and to review and/or editing of the manuscript before submission.

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S. S. Zeki declares that he has received a research grant from the charitable organization CORE. The other authors declare no competing interests.

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Zeki, S., Graham, T. & Wright, N. Stem cells and their implications for colorectal cancer. Nat Rev Gastroenterol Hepatol 8, 90–100 (2011). https://doi.org/10.1038/nrgastro.2010.211

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