Department of General Surgery, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853, China.
Br J Cancer. 2014 Apr 15;110(8):2011-20. doi: 10.1038/bjc.2014.112. Epub 2014 Mar 4.
Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), which is identified as a novel intestinal stem cell marker, is overexpressed in various tumours. In this study, we explore Lgr5 expression in gastric carcinoma and analyse its role in invasion, metastasis, and prognosis in carcinoma.
A combination of immunohistochemistry, western blotting, and quantitative reverse transcription-polymerase chain reaction were used to detect mRNA and protein expression levels of Lgr5 and matrix metalloproteinase 2 (MMP2). Small interfering RNA against Lgr5 was designed, synthesised, and transfected into AGS cells. The effects of Lgr5 siRNA on cell invasion were detected by transwell invasion chamber assay and wound healing assay.
Leucine-rich repeat-containing G-protein-coupled receptor 5 expression was significantly higher in gastric carcinomas than in normal mucosa. Leucine-rich repeat-containing G-protein-coupled receptor 5 expression positively correlated with the depth of invasion, lymph node metastasis, distance of metastasis, and MMP2 expression levels. Multivariate analysis showed that Lgr5 had an independent effect on survival, and that it positively correlated with MMP2. Leucine-rich repeat-containing G-protein-coupled receptor 5 siRNAs inhibited Lgr5 mRNA and protein expression. Transwell assays indicated that these siRNAs resulted in significantly fewer cells migrating through the polycarbonate membrane, and wound healing assay also indicated that siRNAs decreased the migration of cells. Inhibition of Lgr5 resulted in a significant decrease in MMP2 and β-catenin levels compared with those in controls.
Leucine-rich repeat-containing G-protein-coupled receptor 5 was correlated with invasion and metastasis. Leucine-rich repeat-containing G-protein-coupled receptor 5 inhibition could serve as a novel therapeutic approach.
富含亮氨酸重复序列的 G 蛋白偶联受体 5（Lgr5）被鉴定为一种新型的肠道干细胞标志物，在各种肿瘤中过度表达。本研究探讨了 Lgr5 在胃癌中的表达，并分析了其在肿瘤侵袭、转移和预后中的作用。
采用免疫组织化学、Western blot 和实时定量逆转录聚合酶链反应检测 Lgr5 和基质金属蛋白酶 2（MMP2）的 mRNA 和蛋白表达水平。设计并合成针对 Lgr5 的小干扰 RNA（siRNA），转染 AGS 细胞。用 Transwell 侵袭小室实验和划痕愈合实验检测 Lgr5 siRNA 对细胞侵袭的影响。
Lgr5 在胃癌组织中的表达明显高于正常黏膜。Lgr5 的表达与浸润深度、淋巴结转移、远处转移和 MMP2 的表达水平呈正相关。多因素分析显示，Lgr5 对生存有独立影响，与 MMP2 呈正相关。Lgr5 siRNAs 抑制 Lgr5 mRNA 和蛋白表达。Transwell 实验表明，这些 siRNAs 导致穿过聚碳酸酯膜的细胞迁移明显减少，划痕愈合实验也表明 siRNAs 减少了细胞的迁移。与对照组相比，抑制 Lgr5 导致 MMP2 和 β-连环蛋白水平显著降低。
Lgr5 与侵袭和转移相关。抑制 Lgr5 可能成为一种新的治疗方法。
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