Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5 in colorectal cancer
Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5 in colorectal cancer
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DOI：
10.1111/j.1349-7006.2010.01571.x
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发表时间：
2010-07-01
期刊：
影响因子：
5.7
通讯作者：
Sakamoto, Michiie
中科院分区：
文献类型：
--
作者：
Uchida, Hiroshi;Yamazaki, Ken;Sakamoto, Michiie
富含亮氨酸重复序列的G蛋白偶联受体5（LGR 5）是一种7-跨膜受体，据报道在小鼠肠隐窝和毛囊的干细胞中表达。在某些类型的癌症中观察到LGR 5的过表达;然而，在结直肠肿瘤发生中没有特异性评估。我们在37个代表性的癌细胞系中进行了LGR 5表达的定量RT-PCR，结果表明LGR 5 mRNA在结肠癌细胞系中频繁过表达。此外，与来自原发性肿瘤的结肠癌细胞系相比，来自转移性肿瘤的结肠癌细胞系中的LGR 5表达更高。在临床标本中，与匹配的正常粘膜相比，50例结直肠癌（CRC）中有35例LGR 5显著过表达，7例散发性结肠腺瘤中有7例LGR 5过表达。这表明LGR 5在结直肠肿瘤发生的早期阶段上调。LGR 5表达在CRC病例中显示出显著变化，并且与淋巴管浸润、血管浸润、肿瘤深度、淋巴结转移和肿瘤分期（IIIC vs. IIIB）显著相关。除癌细胞外，原位杂交显示小肠和结肠的隐窝基底柱状细胞表达LGR 5。这是第一份报告表明LGR 5不仅参与结直肠肿瘤发生的早期事件，而且参与晚期事件。（Cancer Sci 2010）。
Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a 7-transmembrane receptor reportedly expressed in stem cells of the intestinal crypts and hair follicles of mice. Overexpression of LGR5 is observed in some types of cancer; however, there has been no specific assessment in colorectal tumorigenesis. We performed quantitative RT-PCR for LGR5 expression in 37 representative cancer cell lines, and showed that LGR5 mRNA was frequently overexpressed in colon cancer cell lines. Moreover, LGR5 expression was higher in colon cancer cell lines derived from metastatic tumors compared with those from primary tumors. In clinical specimens, there was significant overexpression of LGR5 in 35 of 50 colorectal cancers (CRCs), and in seven of seven sporadic colonic adenomas, compared with matched normal mucosa. This suggests up-regulation of LGR5 from the early stage of colorectal tumorigenesis. LGR5 expression showed marked variation among CRC cases and correlated significantly with lymphatic invasion, vascular invasion, tumor depth, lymph node metastasis, and tumor stage (IIIC vs. IIIB). In addition to cancer cells, crypt base columnar cells of the small intestine and colon were shown by in situ hybridization to express LGR5. This is the first report suggesting the involvement of LGR5, not only in early events but also in late events in colorectal tumorigenesis. (Cancer Sci 2010).