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Distribution of LGR5+ cells and associated implications during the gastric tumorigenesis
위암 발달 단계에서 LGR5 양성 줄기세포의 분포와 의미 연구

DC Field Value Language
dc.contributor.advisor김우호-
dc.contributor.author장보근-
dc.date.accessioned2017-07-14T01:30:17Z-
dc.date.available2017-07-14T01:30:17Z-
dc.date.issued2015-02-
dc.identifier.other000000024919-
dc.identifier.urihttps://hdl.handle.net/10371/122036-
dc.description학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2015. 2. 김우호.-
dc.description.abstractLgr5 was identified as a promising gastrointestinal tract stem cell marker in mice, and lineage tracing experiments demonstrated that Lgr5+ cells may not only be the cells responsible for the origin of tumors-
dc.description.abstractthey 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 remarkably increased in intestinal metaplasia (IM). In total, 76% of gastric adenomas (GAs) 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 supporting the idea that LGR5+ cells may act as stem cells in GAs. In addition, we found that LGR5 positivity is associated with worse clinical outcomes for the gastric cancer patients with nuclear -catenin expression. However, induced LGR5 overexpression showed no survival benefit in the gastric cancer cell lines. In conclusion, LGR5 positive cells are present at the base of gastric antrum of human, and their population dramatically expands in IM. Most gastric adenomas contain a large number of LGR5-expressing cells, which tend to locate at the base of tumor glands co-expressing other intestinal stem cell markers, suggesting the possibility of LGR5 functioning as tumor stem cells in human gastric adenomas.-
dc.description.tableofcontentsAbstract………………………………………………………………i
Contents……………………………………………………………iii
List of tables…………………………………………………………iv
List of figures………………………………………………………v
Introduction…………………………………………………………2
Material and Methods……………………………………………5
Results
1. RNAscope specifically identifies LGR5+ stem cells in human tissues.
…………………………………………………………………13
2. Intestinal metaplasia in the stomach is associated with a marked expansion of the LGR5+ cell population.
…………………………………………………………………19
3. The LGR5+ cell population specifically increases with IM and positively correlates with CD133 expression.
…………………………………………………………………24
4. LGR5+ tumor cells are often confined to the basal areas of tumor glands, reminiscent of normal stem cell niches.
…………………………………………………………………26
5. LGR5 positivity is associated with nuclear β-catenin, histological differentiation, and mucin type in gastric adenomas.
…………………………………………………………………33
6. LGR5 expression is associated with the levels of other intestinal stem cell (ISC) markers.
…………………………………………………………………38
7. Basal restriction of LGR5+ cells in GAs correlates with the differential expression of ISC markers along the gland axes.
…………………………………………………………………41
8. Spatial correlation of LGR5 expression with ISC markers in gastric adenomas.
…………………………………………………………………43
9. Reduced LGR5 expression in gastric cancers.
…………………………………………………………………48
10. LGR5 is associated with poor survival in gastric cancer patients with nuclear -catenin.
…………………………………………………………………50
11. No effects of LGR5 expression on the growth of gastric cancer cells.
………………………………………………………………54
Discussion……………………………………………………………58
References……………………………………………………………66
Abstract in Korean…………………………………………………73
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dc.formatapplication/pdf-
dc.format.extent3480984 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectLeucine-rich repeat-containing G-coupled Receptor 5 (LGR5)-
dc.subjectcancer stem cell-
dc.subjectgastric tumorigenesis-
dc.subject.ddc610-
dc.titleDistribution of LGR5+ cells and associated implications during the gastric tumorigenesis-
dc.title.alternative위암 발달 단계에서 LGR5 양성 줄기세포의 분포와 의미 연구-
dc.typeThesis-
dc.description.degreeDoctor-
dc.citation.pages73-
dc.contributor.affiliation의과대학 의학과-
dc.date.awarded2015-02-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Ph.D. / Sc.D._의학과)
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