| First Author | Jang BG | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 12 | Pages | e82390 |
| PubMed ID | 24340024 | Mgi Jnum | J:225173 |
| Mgi Id | MGI:5691656 | Doi | 10.1371/journal.pone.0082390 |
| Citation | Jang BG, et al. (2013) Distribution of LGR5+ cells and associated implications during the early stage of gastric tumorigenesis. PLoS One 8(12):e82390 |
| abstractText | 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. |
