Distribution of LGR5
+ Cells and Associated Implications during the Early Stage of Gastric Tumorigenesis |
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Authors: | Bo Gun Jang Byung Lan Lee Woo Ho Kim |
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Institution: | 1. Department of Pathology, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea.; 2. Department of Anatomy, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea.; University Claude Bernard Lyon 1, France, |
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Abstract: | 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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