Amplification and invasiveness of epithelial progenitors during gastric carcinogenesis in trefoil factor 1 knockout mice
Amplification and invasiveness of epithelial progenitors during gastric carcinogenesis in trefoil factor 1 knockout mice
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DOI：
10.1111/j.1365-2184.2008.00562.x
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发表时间：
2008-12-01
影响因子：
8.5
通讯作者：
Rio, M. -C.
中科院分区：
文献类型：
--
作者：
Karam, S. M.;Tomasetto, C.;Rio, M. -C.
目的：幽门窦上皮祖细胞是否参与胃癌的发生尚不清楚。正常情况下，这些祖细胞产生两个主要的细胞谱系：窝和腺粘液细胞。本研究旨在研究三叶因子1（TFF 1）基因敲除小鼠胃腺瘤和胃癌发生过程中幽门窦粘液细胞谱系及其祖细胞的变化。材料与方法：TFF 1基因敲除小鼠的幽门胃窦粘膜组织在3天至17个月的年龄进行了处理，用于组织化学分析，分别使用荆豆和Grifforia lectins作为标记物的小凹和腺粘液细胞。用免疫组织化学和电镜技术鉴定分裂的上皮祖细胞。结果：TFF1的丢失与粘液分泌腺和腺细胞的扩增有关。这两种凝集素不仅与成熟的粘液细胞结合，而且与大多数上皮祖细胞结合，这些祖细胞随着年龄的增长而逐渐扩增，并经常出现在有丝分裂中。对12至17个月大的TFF1缺陷胃的分析显示，在胃窦粘膜的基底部分，偶尔会出现分化不良的粘膜细胞群，其特征与上皮祖细胞（或干细胞）相似。这些细胞最终侵入粘膜肌层，同时保持一定的分化能力。结论：这项研究表明，在TFF 1基因敲除小鼠的幽门窦中，小凹和腺粘液细胞的祖细胞有助于胃癌的发生，强烈支持癌症干细胞起源的概念。
Objective: It is not known whether or not epithelial progenitors of the pyloric antrum are involved in gastric carcinogenesis. Normally, these progenitors give rise to two main cell lineages: pit and gland mucous cells. This study was designed to examine the changes that occur in pyloric antral mucous cell lineages and their progenitors during development of gastric adenoma and carcinoma in trefoil factor 1 (TFF1) knockout mice. Materials and methods: Pyloric antral mucosal tissues of TFF1 knockout mice at ages from 3 days to 17 months were processed for histochemical analysis using Ulex europaeus and Grifforia simplifolica lectins as markers for pit and gland mucous cells, respectively. The dividing epithelial progenitors were identified by using immunohistochemical and electron microscopy techniques. Results: TFF1 loss was associated with amplification of both mucus-secreting pit and gland cells. Both lectins examined bound not only to mature mucous cells, but also to most of epithelial progenitors which gradually amplified with age and frequently were seen in mitosis. Analysis of 12- to 17-month-old TFF1-deficient stomachs revealed occasional groups of poorly differentiated mucosal cells with features similar to those of epithelial progenitors (or stem cells), in the basal portion of the antral mucosa. These cells eventually invaded the muscularis mucosa while maintaining some capacity to differentiate. Conclusion: This study shows that the progenitors of pit and gland mucous cells contribute to gastric carcinogenesis in the pyloric antrum of TFF1 knockout mice, strongly supporting the concept of stem cell origin of cancer.