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. 2014 Aug 15;5(3):366-72.
doi: 10.4291/wjgp.v5.i3.366.

Cancer stem cells in Helicobacter pylori infection and aging: Implications for gastric carcinogenesis

Edi Levi  1 , Paula Sochacki  1 , Nabiha Khoury  1 , Bhaumik B Patel  1 , Adhip Pn Majumdar  1
Affiliations

Cancer stem cells in Helicobacter pylori infection and aging: Implications for gastric carcinogenesis

Edi Levi et al. World J Gastrointest Pathophysiol. .

Abstract

Aim: To demonstrated the combined effects of aging and carcinogen treatment on cancer stem/stem-like cells (CSCs) of gastric mucosa in an animal model.

Methods: In this study we investigated the effects of aging and Helicobacter pylori (H. pylori) inflammation as a model for inflammation induced carcinogenesis in human and rat gastric mucosa samples. In aging studies, we compared 4-mo old (young) with 22 mo (aged) old Fischer-344 rats. For human studies, gastric biopsies and resection specimens representing normal mucosa or different stages of H. pylori gastritis and gastric adenocarcinomas were used for determining the expression of stem cell markers CD166, ALDH1 and LGR5. In addition we performed immunofluorescent double labeling for B-catenin and Lgr5 in both rat and human gastric tissues to examine the status of Wnt signaling in these cells.

Results: CSC markers ALDH1, LGR5, and CD166 were expressed in very low levels in normal human gastric mucosa or young rat gastric mucosa. In contrast, level of expression for all three markers significantly increased in H. pylori gastritis and gastric adenocarcinomas as well as in normal gastric mucosa in aged rats. We also observed cytoplasmic B-catenin staining in both aged rat and human H. pylori inflamed gastric mucosa, which were found to be colocalized with Lgr5 immunoreactive cells. The increased number of ALDH1, CD166 and LGR5 positive cells in H. pylori gastritis indicates that increased number of stem-like cells in gastric mucosa is an early event, and may constitute an important step in the progression to neoplasia.

Conclusion: Our observation of the age-related increase in cancer stem/stem-like cells in the gastric mucosa may explain the increased incidence of gastric cancer during aging. Combination of aging and H. pylori infection may have additive effects in progression to neoplasia.

Keywords: ALDH1; Aging; CD166; Cancer stem cells; Gastric cancer; Helicobacter pylori; LGR5.

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Figures

Figure 1
Figure 1
Higher expression of B-catenin, CD166, and LGR5 in normal aged rat gastric mucosa, compared to young rat normal gastric mucosa is demonstrated. × 200 magnification. A: 4 m CD166; B: 24 m CD166; C: 4 m LGR5; D: 24 m LGR5; E: 4 m B-catenin; F: 24 m B-catenin.
Figure 2
Figure 2
Double labeling for LGR5 (green, left panel) and B-catenin (red, right panel) in aged rat gastric mucosa (Lower Panel, × 600 magnification), H. pylori infected human gastric mucosa (Upper Panel, × 400 magnification) shows cytoplasmic localization of B-catenin in an LGR5 expressing cell.
Figure 3
Figure 3
Immunohistochemical staining of stem cell markers ALDH1, CD166, LGR5 in human normal gastric mucosa, gastric mucosa with H. pylori gastritis, and gastric adenocarcinoma, demonstrates increased expression of each of the markers over the normal controls. × 200 magnification. A: ALDH1 Normal; B: ALDH1 HP; C: ALDH1 CA; D: CD166 Normal; E: CD166 HP; F: CD166 CA; G: LGR5 Normal; H: LGR5 HP; I: LGR5 CA.
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