Mutoh Hiroyuki, Sashikawa Miho, Sakamoto Hirotsugu, Tateno Tomoko
Division of Gastroenterology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
Gut Liver. 2014 Sep;8(5):508-18. doi: 10.5009/gnl13237. Epub 2014 Apr 23.
BACKGROUND/AIMS: Doublecortin and CaM kinase-like-1 (DCAMKL1) is a marker of stem cells expressed predominantly in the crypt base in the intestine. However, DCAMKL1-positive cells have been shown to be differentiated tuft cells rather than quiescent progenitors. Tuft cells are the only epithelial cells that express cyclooxygenase 2 (COX-2) in the normal intestinal epithelium. We previously generated Cdx2-transgenic mice as model mice for intestinal metaplasia and gastric carcinoma. In the current study, we investigated the association between COX-2 and DCAMKL1 in gastric carcinoma.
We examined the association between COX-2 and DCAMKL1 expression in gastric carcinomas in clinical samples (early gastric well-differentiated adenocarcinoma) and Cdx2-transgenic mice; and the DCAMKL1-transgenic mouse stomach using immunohistochemistry and quantitative real-time polymerase chain reaction.
The COX-2-expressing cells were scattered, not diffusely expressed, in gastric carcinomas from humans and Cdx2-transgenic mice. DCAMKL1-positive cells were also scattered in the gastric carcinomas, indicating that tuft cells could still be present in gastric carcinoma. COX-2 was expressed in DCAMKL1-positive tuft cells in Cdx2- and DCAMKL1-transgenic mouse stomachs, whereas the Sox9 transcription factor was ubiquitously expressed in gastric carcinomas, including COX-2-positive cells.
COX-2 is expressed in DCAMKL1-expressing quiescent tuft cells in gastric carcinoma.
背景/目的:双皮质素和钙调蛋白激酶样蛋白1(DCAMKL1)是干细胞的标志物,主要在肠道隐窝底部表达。然而,DCAMKL1阳性细胞已被证明是分化的簇状细胞而非静止的祖细胞。簇状细胞是正常肠上皮中唯一表达环氧化酶2(COX-2)的上皮细胞。我们之前构建了Cdx2转基因小鼠作为肠化生和胃癌的模型小鼠。在本研究中,我们调查了胃癌中COX-2与DCAMKL1之间的关联。
我们使用免疫组织化学和定量实时聚合酶链反应,检测了临床样本(早期胃高分化腺癌)和Cdx2转基因小鼠胃癌中COX-2与DCAMKL1表达之间的关联;以及DCAMKL1转基因小鼠胃中的情况。
在人类和Cdx2转基因小鼠的胃癌中,表达COX-2的细胞呈散在分布,而非弥漫性表达。DCAMKL1阳性细胞在胃癌中也呈散在分布,表明簇状细胞仍可能存在于胃癌中。在Cdx2和DCAMKL1转基因小鼠胃中,COX-2在DCAMKL1阳性簇状细胞中表达,而Sox9转录因子在包括COX-2阳性细胞在内的胃癌中普遍表达。
COX-2在胃癌中表达DCAMKL1的静止簇状细胞中表达。