The spatial distribution of LGR5+ cells correlates with gastric cancer progression.
The spatial distribution of LGR5+ cells correlates with gastric cancer progression.
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DOI：
10.1371/journal.pone.0035486
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Röcken C
中科院分区：
文献类型：
--
作者：
Simon E;Petke D;Böger C;Behrens HM;Warneke V;Ebert M;Röcken C
在这项研究中，我们测试了Wnt靶蛋白和癌症干细胞标志物LGR 5在人类胃肠道肿瘤中的患病率、组织解剖学分布和肿瘤生物学意义。在转录（实时聚合酶链反应）和翻译水平（免疫组织化学）上研究了127名患者的恶性和相应的非恶性组织中LGR 5的差异表达，所述患者包括六个不同的原发性肿瘤部位，即食管、胃、肝、胰腺、结肠和直肠。研究100例胃癌组织中LGR 5表达的临床病理意义。非肿瘤组织通常仅含有非常少的分散的LGR 5+细胞。与相应的非肿瘤组织相比，食管、胃、肝、胰腺、结肠和直肠的相应癌显示出显著更多的LGR 5+细胞以及显著更高水平的LGR 5-mRNA。双染色实验揭示了LGR 5与假定的干细胞标志物CD 44、Musashi-1和ADAM 17的共表达。接下来，我们测试了胃癌发生的顺序变化，即慢性萎缩性胃炎、肠上皮化生和浸润性癌，与LGR 5+细胞的重新分配相关的假设。有趣的是，LGR 5的空间分布发生了变化：在非肿瘤性胃粘膜中，LGR 5+细胞主要存在于粘液颈部区域;在肠上皮化生中，LGR 5+细胞定位于隐窝基部，而在GC中，LGR 5+细胞存在于腔表面、肿瘤中心和浸润前沿。LGR 5在胃癌中心和浸润前沿的表达与局部肿瘤生长（T-类）和淋巴结扩散（N-类）显著相关。此外，LGR 5 + GC患者的中位生存期（28.0±8.6个月）短于LGR 5 − GC患者（54.5±6.3个月）。我们的研究结果表明，LGR 5在胃肠道肿瘤中差异表达，并且当寻求其肿瘤生物学意义时，必须考虑LGR 5+细胞的空间组织解剖分布。
In this study we tested the prevalence, histoanatomical distribution and tumour biological significance of the Wnt target protein and cancer stem cell marker LGR5 in tumours of the human gastrointestinal tract. Differential expression of LGR5 was studied on transcriptional (real-time polymerase chain reaction) and translational level (immunohistochemistry) in malignant and corresponding non-malignant tissues of 127 patients comprising six different primary tumour sites, i.e. oesophagus, stomach, liver, pancreas, colon and rectum. The clinico-pathological significance of LGR5 expression was studied in 100 patients with gastric carcinoma (GC). Non-neoplastic tissue usually harboured only very few scattered LGR5+ cells. The corresponding carcinomas of the oesophagus, stomach, liver, pancreas, colon and rectum showed significantly more LGR5+ cells as well as significantly higher levels of LGR5-mRNA compared with the corresponding non-neoplastic tissue. Double staining experiments revealed a coexpression of LGR5 with the putative stem cell markers CD44, Musashi-1 and ADAM17. Next we tested the hypothesis that the sequential changes of gastric carcinogenesis, i.e. chronic atrophic gastritis, intestinal metaplasia and invasive carcinoma, are associated with a reallocation of the LGR5+ cells. Interestingly, the spatial distribution of LGR5 changed: in non-neoplastic stomach mucosa, LGR5+ cells were found predominantly in the mucous neck region; in intestinal metaplasia LGR5+ cells were localized at the crypt base, and in GC LGR5+ cells were present at the luminal surface, the tumour centre and the invasion front. The expression of LGR5 in the tumour centre and invasion front of GC correlated significantly with the local tumour growth (T-category) and the nodal spread (N-category). Furthermore, patients with LGR5+ GCs had a shorter median survival (28.0±8.6 months) than patients with LGR5− GCs (54.5±6.3 months). Our results show that LGR5 is differentially expressed in gastrointestinal cancers and that the spatial histoanatomical distribution of LGR5+ cells has to be considered when their tumour biological significance is sought.
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影响因子：
3.1
作者：
Nishimura, S;Wakabayashi, N;Mitsufuji, S
通讯作者：
Mitsufuji, S
影响因子：
3.6
作者：
McClanahan, Terrill;Koseoglu, Sandra;Samatar, Ahmed A.
通讯作者：
Samatar, Ahmed A.
影响因子：
2.8
作者：
Fan, Xiang-Shan;Wu, Hong-Yan;Huang, Qin
通讯作者：
Huang, Qin
DOI：
10.1007/978-1-61779-145-1_18
发表时间：
2011-01-01
期刊：
STEM CELL MIGRATION: METHODS AND PROTOCOLS
影响因子：
--
作者：
Draheim, Kyle M.;Lyle, Stephen
通讯作者：
Lyle, Stephen
影响因子：
3.2
作者：
Fanjul, Marjorie;Gmyr, Valery;Hollande, Etienne
通讯作者：
Hollande, Etienne