Intestinal stem cell marker LGR5 expression during gastric carcinogenesis

Zheng, Zhixue; Sun, Yu; Bu, Zhaode; Zhang, Lianhai; Li, Ziyu; Wu, Aiwen; Wu, Xiaojiang; Wang, Xiaohong; Cheng, Xiaoxing; Xing, Xiaofang; Du, Hong; Ji, Jiafu

doi:10.3748/wjg.v19.i46.8714

Cited by 32 publications

(34 citation statements)

References 43 publications

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“…It found that patients with gastric cancer and H pylori infection had an expanded pool of LGR5 + stem cells in the antrum, and higher amounts of DNA oxidative damage in these stem cells 111 . Several other studies have confirmed that levels of LGR5 mRNA and protein are increased in stomach tissues from patients with gastric cancer 112, 113 . Higher levels of LGR5 may be a marker of poor prognosis for patients with gastric cancer 114 .…”

Section: Effects On Gastric Stem Cellsmentioning

confidence: 75%

Pathobiology of Helicobacter pylori–Induced Gastric Cancer

2016

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Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data indicate that subtle mismatches between host and microbe genetic traits greatly affect risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness demonstrates the sophisticated relationship among H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori’s activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism.

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Section: Effects On Gastric Stem Cellsmentioning

confidence: 75%

Pathobiology of Helicobacter pylori–Induced Gastric Cancer

2016

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“…There was no correlation between Lgr5 expression and the clinicopathological variables examined in our study. In contrast, previous studies have identified a positive correlation between Lgr5 expression and depth of tumor invasion, lymph node metastasis, and distant metastasis in invasive gastric carcinoma . Another study has reported a positive association between Lgr5 expression and age, tumor differentiation, Lauren type, and TNM stage .…”

Section: Discussionmentioning

confidence: 65%

“…In contrast, previous studies have identified a positive correlation between Lgr5 expression and depth of tumor invasion, lymph node metastasis, and distant metastasis in invasive gastric carcinoma. 17,18 Another study has reported a positive association between Lgr5 expression and age, tumor differentiation, Lauren type, and TNM stage. 17 Furthermore, recent investigations have demonstrated that patients expressing Lgr5 have a worse prognosis than those that do not.…”

Section: Discussionmentioning

confidence: 99%

Distribution of Lgr5‐positive cancer cells in intramucosal gastric signet‐ring cell carcinoma

Nakajima

Uehara

Maruyama

et al. 2016

Pathology International

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Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is a putative intestinal stem cell marker that is also expressed in various tumors. To analyze its pathological characteristics in mucosal gastric signet-ring cell carcinoma (SRCC), we investigated Lgr5 expression in 35 intramucosal gastric SRCC patients using RNAscope, a newly developed RNA in situ hybridization technique. Lgr5 expression in individual tumor cells was scored semi-quantitatively from 0 to 400. Ki67 was also examined by immunohistochemistry, with a linear arrangement of Ki67-expressing cells present in 20 of 35 cases. This area of Ki67-expressing cells was topographically divided into upper, middle, and lower regions. All cases with linear Ki67 expression patterns also had Lgr5-positive cells arranged in a linear fashion in the lower area-which was distinct from the area of high Ki67 expression. The rate of Ki67 positivity in Lgr5-positive cells was significantly lower than that of Lgr5-negative cells in areas of high Ki67 expression. In intramucosal SRCC, the low mitotic activity of Lgr5-positive cells suggests that they may represent cancer stem cells as seen in other types of stomach carcinomas. Intramucosal SRCC may therefore contain stem cells expressing Lgr5 in the lower area of the lamina propria, akin to normal gastric pyloric mucosa.

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“…There is clinical evidence for a role of Lgr5+ cells in the carcinogenesis of GC [29][30][31][32]. However, most of thise evidence come from the analyses on the clinical samples.…”

Section: Discussionmentioning

confidence: 99%

“…In stomach, Lgr5+ stem cells drive self-renewal and can build long-lived gastric units in vitro [28]. Helicobacter pylori infection has been associated with the increases in Lgr5-positive cells in the stomach of patients with gastric cancer, and been hypothesized to relate to gastric carcinogenesis, based on clinical data [29][30][31][32]. However, the role of Lgr5-positive cells in GC has not been extensively tested for their CSC characteristics in vitro using molecular biological methods.…”

Section: Introductionmentioning

confidence: 99%

Lgr5-Positive Cells are Cancer-Stem-Cell-Like Cells in Gastric Cancer

Wang

Liu

2015

Cell Physiol Biochem

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Background/Aims: Effective treatment of gastric cancer (GC) requires better understanding of the molecular regulation of its carcinogenesis. Identification of cancer stem cells (CSCs) in GC appears to be a critical question. Methods: We analyzed Lgr5 expression in GC specimen. We used an adeno-associated virus (AAV) that carries diphtheria toxin fragment A (DTA) under the control of Lgr5 promoter (AAV-pLgr5-DTA) to transduce human GC cells. The growth of GC cells with/without depletion of Lgr5-positive cells was studied in vitro in an MTT assay, and in vivo by analyzing bioluminescence levels. Results: A portion of GC cells in the resected specimen expressed Lgr5. GC cells that formed tumor spheres expressed high Lgr5. Selective depletion of Lgr5-positive GC cells resulted in significant growth inhibition of GC cells in vitro and in vivo. Conclusion: Lgr5-positive cells may be CSCs-like cells in GC and may play a pivotal role in the tumorigenesis of GC. Treating Lgr5-positive GC cells may substantially improve the therapeutic outcome.

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Intestinal stem cell marker LGR5 expression during gastric carcinogenesis

Abstract: Enhanced LGR5 is related to progressive dedifferentiation and metastasis of gastric cancer, indicating the potential of this receptor as an early diagnostic and prognostic biomarker.

Cited by 32 publications

References 43 publications

Pathobiology of Helicobacter pylori–Induced Gastric Cancer

Pathobiology of Helicobacter pylori–Induced Gastric Cancer

Distribution of Lgr5‐positive cancer cells in intramucosal gastric signet‐ring cell carcinoma

Lgr5-Positive Cells are Cancer-Stem-Cell-Like Cells in Gastric Cancer

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