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Distribution of LGR5 (+) Cells and Associated Implications during the Early Stage of Gastric Tumorigenesis

Lgr5 was identified as a promising gastrointestinal tract stem cell marker in mice. Lineage tracing indicates that Lgr5 (+) cells may not only be the cells responsible for the origin of tumors; they may also be the so-called cancer stem cells. In the present study, we investigated the presence of Lg...

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Detalles Bibliográficos
Autores principales: Jang, Bo Gun, Lee, Byung Lan, Kim, Woo Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858308/
https://www.ncbi.nlm.nih.gov/pubmed/24340024
http://dx.doi.org/10.1371/journal.pone.0082390
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author Jang, Bo Gun
Lee, Byung Lan
Kim, Woo Ho
author_facet Jang, Bo Gun
Lee, Byung Lan
Kim, Woo Ho
author_sort Jang, Bo Gun
collection PubMed
description Lgr5 was identified as a promising gastrointestinal tract stem cell marker in mice. Lineage tracing indicates that Lgr5 (+) cells may not only be the cells responsible for the origin of tumors; they may also be the so-called cancer stem cells. In the present study, we investigated the presence of Lgr5 (+) cells and their biological significance in normal human gastric mucosa and gastric tumors. RNAscope, a newly developed RNA in situ hybridization technique, specifically labeled Lgr5 (+) cells at the basal glands of the gastric antrum. Notably, the number of Lgr5 (+) cells was remarkably increased in intestinal metaplasia. In total, 76% of gastric adenomas and 43% of early gastric carcinomas were positive for LGR5. Lgr5 (+) cells were found more frequently in low-grade tumors with active Wnt signaling and an intestinal gland type, suggesting that LGR5 is likely involved in the very early stages of Wnt-driven tumorigenesis in the stomach. Interestingly, similar to stem cells in normal tissues, Lgr5 (+) cells were often restricted to the base of the tumor glands, and such Lgr5 (+) restriction was associated with high levels of intestinal stem cell markers such as EPHB2, OLFM4, and ASCL2. Thus, our findings show that Lgr5 (+) cells are present at the base of the antral glands in the human stomach and that this cell population significantly expands in intestinal metaplasias. Furthermore, Lgr5 (+) cells are seen in a large number of gastric tumors ; their frequent basal arrangements and coexpression of ISC markers support the idea that Lgr5 (+) cells act as stem cells during the early stage of intestinal-type gastric tumorigenesis.
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spelling pubmed-38583082013-12-11 Distribution of LGR5 (+) Cells and Associated Implications during the Early Stage of Gastric Tumorigenesis Jang, Bo Gun Lee, Byung Lan Kim, Woo Ho PLoS One Research Article Lgr5 was identified as a promising gastrointestinal tract stem cell marker in mice. Lineage tracing indicates that Lgr5 (+) cells may not only be the cells responsible for the origin of tumors; they may also be the so-called cancer stem cells. In the present study, we investigated the presence of Lgr5 (+) cells and their biological significance in normal human gastric mucosa and gastric tumors. RNAscope, a newly developed RNA in situ hybridization technique, specifically labeled Lgr5 (+) cells at the basal glands of the gastric antrum. Notably, the number of Lgr5 (+) cells was remarkably increased in intestinal metaplasia. In total, 76% of gastric adenomas and 43% of early gastric carcinomas were positive for LGR5. Lgr5 (+) cells were found more frequently in low-grade tumors with active Wnt signaling and an intestinal gland type, suggesting that LGR5 is likely involved in the very early stages of Wnt-driven tumorigenesis in the stomach. Interestingly, similar to stem cells in normal tissues, Lgr5 (+) cells were often restricted to the base of the tumor glands, and such Lgr5 (+) restriction was associated with high levels of intestinal stem cell markers such as EPHB2, OLFM4, and ASCL2. Thus, our findings show that Lgr5 (+) cells are present at the base of the antral glands in the human stomach and that this cell population significantly expands in intestinal metaplasias. Furthermore, Lgr5 (+) cells are seen in a large number of gastric tumors ; their frequent basal arrangements and coexpression of ISC markers support the idea that Lgr5 (+) cells act as stem cells during the early stage of intestinal-type gastric tumorigenesis. Public Library of Science 2013-12-10 /pmc/articles/PMC3858308/ /pubmed/24340024 http://dx.doi.org/10.1371/journal.pone.0082390 Text en © 2013 Jang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Jang, Bo Gun
Lee, Byung Lan
Kim, Woo Ho
Distribution of LGR5 (+) Cells and Associated Implications during the Early Stage of Gastric Tumorigenesis
title Distribution of LGR5 (+) Cells and Associated Implications during the Early Stage of Gastric Tumorigenesis
title_full Distribution of LGR5 (+) Cells and Associated Implications during the Early Stage of Gastric Tumorigenesis
title_fullStr Distribution of LGR5 (+) Cells and Associated Implications during the Early Stage of Gastric Tumorigenesis
title_full_unstemmed Distribution of LGR5 (+) Cells and Associated Implications during the Early Stage of Gastric Tumorigenesis
title_short Distribution of LGR5 (+) Cells and Associated Implications during the Early Stage of Gastric Tumorigenesis
title_sort distribution of lgr5 (+) cells and associated implications during the early stage of gastric tumorigenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858308/
https://www.ncbi.nlm.nih.gov/pubmed/24340024
http://dx.doi.org/10.1371/journal.pone.0082390
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