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Review
. 2018 Oct 31;6(4):100.
doi: 10.3390/biomedicines6040100.

Gastric Stem Cell and Cellular Origin of Cancer

Masahiro Hata  1 , Yoku Hayakawa  2 , Kazuhiko Koike  3
Affiliations
Review

Gastric Stem Cell and Cellular Origin of Cancer

Masahiro Hata et al. Biomedicines. .

Abstract

Several stem cell markers within the gastrointestinal epithelium have been identified in mice. One of the best characterized is Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) and evidence suggests that Lgr5+ cells in the gut are the origin of gastrointestinal cancers. Reserve or facultative stem or progenitor cells with the ability to convert to Lgr5+ cells following injury have also been identified. Unlike the intestine, where Lgr5+ cells at the crypt base act as active stem cells, the stomach may contain unique stem cell populations, since gastric Lgr5+ cells seem to behave as a reserve rather than active stem cells, both in the corpus and in the antral glands. Gastrointestinal stem cells are supported by a specific microenvironment, the stem cell niche, which also promotes tumorigenesis. This review focuses on stem cell markers in the gut and their supporting niche factors. It also discusses the molecular mechanisms that regulate stem cell function and tumorigenesis.

Keywords: Lgr5; Mist1; gastric cancer; gastric stem cell; stem cell; stem cell niche.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schema of murine gastric glands and cell types. In the corpus glands (left), stem and transit-amplifying (TA) progenitor cells reside within the isthmus, and supply mature cell types including surface pit cells, parietal cells, neck cells, tuft cells, enterochromaffin-like (ECL) cells, and chief cells. Mist1, Troy, and Runx1 enhancer element (eR1) are expressed in both stem and chief cells, while Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) expression is normally restricted in chief cells. However, following high-dose tamoxifen-induced damage, aberrant Lgr5 expression is observed within the isthmus. In the antrum (right), there are two distinct stem cell populations; one expresses Lgr5 at the base, the other expresses Sox2, Lrig1, Mist1, eR1, or Cckbr (cholecystokinin B receptor) within the isthmus, and is more proliferative. Axin2 and Cxcr4 are expressed in both populations. R-spondin activates antral isthmal stem cells but inhibits Lgr5 expressing stem cells.
See this image and copyright information in PMC

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