Anat Cell Biol.  2013 Mar;46(1):8-18. 10.5115/acb.2013.46.1.8.

Gastric stem cells and gastric cancer stem cells

• Han ME
• Oh SO

• KMID: 2046753
• DOI: http://doi.org/10.5115/acb.2013.46.1.8

Abstract

The gastric epithelium is continuously regenerated by gastric stem cells, which give rise to various kinds of daughter cells, including parietal cells, chief cells, surface mucous cells, mucous neck cells, and enteroendocrine cells. The self-renewal and differentiation of gastric stem cells need delicate regulation to maintain the normal physiology of the stomach. Recently, it was hypothesized that cancer stem cells drive the cancer growth and metastasis. In contrast to conventional clonal evolution hypothesis, only cancer stem cells can initiate tumor formation, self-renew, and differentiate into various kinds of daughter cells. Because gastric cancer can originate from gastric stem cells and their self-renewal mechanism can be used by gastric cancer stem cells, we review here how critical signaling pathways, including hedgehog, Wnt, Notch, epidermal growth factor, and bone morphogenetic protein signaling, may regulate the self-renewal and differentiation of gastric stem cells and gastric cancer stem cells. In addition, the precancerous change of the gastric epithelium and the status of isolating gastric cancer stem cells from patients are reviewed.

Keyword

Gastric stem cell; Gastric cancer stem cell; Self-renewal; Cell differentiation

MeSH Terms

Bone Morphogenetic Proteins
Cell Differentiation
Clonal Evolution
Enteroendocrine Cells
Epidermal Growth Factor
Epithelium
Hedgehogs
Humans
Neck
Neoplasm Metastasis
Neoplastic Stem Cells
Nuclear Family
Stem Cells
Stomach
Stomach Neoplasms
Bone Morphogenetic Proteins
Epidermal Growth Factor

Figure

• 

  Fig. 1 Self-renewal and differentiation of gastric stem cells. Gastric stem cells have the capacity to self-renew and to differentiate into various kinds of daughter cells, including surface mucous cells, mucous neck cells, chief cells, and parietal cells. Critical signaling pathways for each differentiation route are indicated in blue. Characteristic genes for each of the differentiated cells are indicated in orange. Arf1, ADP-ribosylation factor 1; BMP, bone morphogenetic protein; Calm2, calmodulin 2; Cdhr5, cadherin-related family member5; EGF, epidermal growth factor; Fads1, fatty acid desaturase 1; FoxQ1, forkhead box Q1; Gif, gastric intrinsic factor; Gkn1, gastrokine-1; Ihh, Indian hedgehog; Igfbp2, insulin-like growth factor binding protein 2; Mist1, basic helix-loop-helix transcription factor; Muc5AC, mucin 5AC; Muc6, mucin 6; Notch, Notch signaling pathway; Pgc, pepsinogen C; Pthlh, parathyroid hormone-like hormone; RA, retinoic acid; Shh, sonic hedgehog; Sod2, superoxide dismutase 2; Tff1, trefoil factor family 1; Tff2, trefoil factor family 2; Wnt, Wnt signaling pathway.

• 

  Fig. 2 (A-D) Electron microscope images of gastric cancer stem cells. Seven days after the single-cell culture, images were taken using a scanning electron microscope (Hitachi S3500N). Note the cavities inside the cancer spheres (A, ×180; B-D, ×1,500). Scale bars=200 µm (A), 30 µm (B-D).

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