Distribution of LGR5+ cells and associated implications during the early stage of gastric tumorigenesis.
Distribution of LGR5+ cells and associated implications during the early stage of gastric tumorigenesis.
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DOI：
10.1371/journal.pone.0082390
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kim WH
中科院分区：
文献类型：
--
作者：
Jang BG;Lee BL;Kim WH
lgr 5被认为是一种有前途的小鼠胃肠道干细胞标志物。谱系追踪表明，Lgr 5+细胞可能不仅是负责肿瘤起源的细胞;它们也可能是所谓的癌症干细胞。在本研究中，我们研究了Lgr 5+细胞的存在及其在正常人胃粘膜和胃肿瘤中的生物学意义。RNAscope是一种新发展的RNA原位杂交技术，可特异性标记胃窦基底腺的Lgr 5+细胞。值得注意的是，Lgr 5+细胞的数量在肠上皮化生中显著增加。总的来说，76%的胃腺瘤和43%的早期胃癌呈LGR 5阳性。LGR 5+细胞在具有活跃Wnt信号传导和肠腺类型的低级别肿瘤中更常见，这表明LGR 5可能参与胃中Wnt驱动的肿瘤发生的非常早期阶段。有趣的是，与正常组织中的干细胞类似，Lgr 5+细胞通常局限于肿瘤腺体的基底，并且这种Lgr 5+限制与高水平的肠干细胞标志物如EPHB 2，OLFM 4和ASCL 2相关。因此，我们的研究结果表明，Lgr 5+细胞存在于人胃窦腺的底部，并且该细胞群在肠化生中显着扩增。此外，Lgr 5+细胞被认为是在大量的胃肿瘤，其频繁的基础安排和ISC标志物的共表达支持的想法，Lgr 5+细胞作为干细胞在胃肠道型胃癌发生的早期阶段。
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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影响因子：
24.5
作者：
Lewis A;Segditsas S;Deheragoda M;Pollard P;Jeffery R;Nye E;Lockstone H;Davis H;Clark S;Stamp G;Poulsom R;Wright N;Tomlinson I
通讯作者：
Tomlinson I
影响因子：
6
作者：
Lennerz, Jochen K. M.;Kim, Seok-Hyung;Mills, Jason C.
通讯作者：
Mills, Jason C.
DOI：
10.1073/pnas.1113890109
发表时间：
2012-03-06
影响因子：
11.1
作者：
Kim, Tae-Hee;Escudero, Silvia;Shivdasani, Ramesh A.
通讯作者：
Shivdasani, Ramesh A.
影响因子：
2.8
作者：
Fan, Xiang-Shan;Wu, Hong-Yan;Huang, Qin
通讯作者：
Huang, Qin
影响因子：
23.9
作者：
Merlos-Suarez, Anna;Barriga, Francisco M.;Batlle, Eduard
通讯作者：
Batlle, Eduard