PDF(Pubmed)
Abstract：
Tuft cells are chemosensory cells associated with luminal homeostasis, immune response, and tumorigenesis in the gastrointestinal tract. We aimed to elucidate alterations in tuft cell populations during gastric atrophy and tumorigenesis in humans with correlative comparison to relevant mouse models. Tuft cell distribution was determined in human stomachs from organ donors and in gastric pathologies including Ménétrier\'s disease, Helicobacter pylori gastritis, intestinal metaplasia (IM), and gastric tumors. Tuft cell populations were examined in Lrig1-KrasG12D , Mist1-KrasG12D , and MT-TGFα mice. Tuft cells were evenly distributed throughout the entire normal human stomach, primarily concentrated in the isthmal region in the fundus. Ménétrier\'s disease stomach showed increased tuft cells. Similarly, Lrig1-Kras mice and mice overexpressing TGFα showed marked foveolar hyperplasia and expanded tuft cell populations. Human stomach with IM or dysplasia also showed increased tuft cell numbers. Similarly, Mist1-Kras mice had increased numbers of tuft cells during metaplasia and dysplasia development. In human gastric cancers, tuft cells were rarely observed, but showed positive associations with well-differentiated lesions. In mouse gastric cancer xenografts, tuft cells were restricted to dysplastic well-differentiated mucinous cysts and were lost in less differentiated cancers. Taken together, tuft cell populations increased in atrophic human gastric pathologies, metaplasia, and dysplasia, but were decreased in gastric cancers. Similar findings were observed in mouse models, suggesting that, while tuft cells are associated with precancerous pathologies, their loss is most associated with the progression to invasive cancer.
摘要：
簇绒细胞是与腔内稳态相关的化学感觉细胞，免疫反应，和胃肠道的肿瘤发生。我们旨在通过与相关小鼠模型的相关比较，阐明人类胃萎缩和肿瘤发生过程中簇绒细胞种群的变化。Tuft细胞分布在人类胃的器官供体和胃病，包括Ménétrier病，幽门螺杆菌胃炎，肠上皮化生（IM），和胃肿瘤.在Lrig1-KrasG12D中检查了簇绒细胞群，Mist1-KrasG12D,和MT-TGFα小鼠。簇状细胞均匀分布在整个正常人的胃中，主要集中在眼底的峡部。Ménétrier的疾病胃显示出增加的簇细胞。同样，Lrig1-Kras小鼠和过表达TGFα的小鼠显示出明显的小窝增生和簇绒细胞群扩大。患有IM或发育不良的人胃也显示出增加的簇细胞数量。同样，Mist1-Kras小鼠在化生和异型增生发育过程中簇绒细胞数量增加。在人类胃癌中，很少观察到簇绒细胞，但与分化良好的病变呈正相关.在小鼠胃癌异种移植物中，簇绒细胞仅限于发育不良的高分化粘液性囊肿，在分化较低的癌症中丢失。一起来看,在萎缩性人类胃病中，簇绒细胞数量增加，化生,和发育不良,但在胃癌中有所下降。在小鼠模型中观察到类似的发现，这表明，虽然簇绒细胞与癌前病变有关，它们的损失与进展为浸润性癌最相关。
