The Cellular Origin of Barrett's Esophagus and Its Stem Cells.
The Cellular Origin of Barrett's Esophagus and Its Stem Cells.
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DOI：
10.1007/978-3-030-11096-3_5
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发表时间：
2019
影响因子：
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通讯作者：
W. Xian;M. Duleba;Yanting Zhang;Yusuke Yamamoto;K. Ho;C. Crum;F. McKeon
中科院分区：
文献类型：
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作者：
W. Xian;M. Duleba;Yanting Zhang;Yusuke Yamamoto;K. Ho;C. Crum;F. McKeon
食管腺癌的发病率在西方国家迅速增加。尽管引进了复杂的内窥镜技术，我们也有能力随时监测被称为巴雷特食管的假定前驱病变。包括射频消融（RFA）和光动力学疗法（PDT）在内的先发制人的方法治疗巴雷特食管和异型增生正在取得引人注目的初步结果。虽然这些非特异性消融治疗的长期疗效有待纵向研究，复发的报告正在增加。更有针对性的治疗，特别是针对巴雷特食管的干细胞，需要了解这种肠上皮化生（IM）的起源。流行的观点认为，巴雷特食管是由食管干细胞的“transcommitment”产生的一种上皮细胞样上皮。另一种解释来自于发现正常个体胃食管交界处存在离散的残留胚胎细胞（RECs），其扩张并定植于慢性反流剥脱的食管区域。这些RECs在食管损伤后数天内形成IM，提示了一种新的肿瘤发生机制。这项工作的一个推论是Barrett's干细胞与鳞状上皮细胞不同，一旦被识别，将形成新的先发制人的策略来解决Barrett's及其相关肿瘤的基础。
The incidence of esophageal adenocarcinoma is rapidly increasing in Western countries. This is despite the introduction of sophisticated endoscopic techniques and our ability to readily monitor the presumed precursor lesion known as Barrett’s esophagus. Preemptive approaches, including radiofrequency ablation (RFA), and photodynamic therapy (PDT) for Barrett’s esophagus and dysplasia are achieving dramatic initial results. Although the long-term efficacy of these nonspecific ablative therapies is awaiting longitudinal studies, reports of recurrences are increasing. More targeted therapies, particularly directed at the stem cells of Barrett’s esophagus, demand knowing the origin of this intestinal metaplasia (IM). The prevailing concept holds that Barrett’s esophagus arises from the “transcommitment” of esophageal stem cells to produce an intestine-like epithelium. An alternative explanation derives from the discovery of a discrete population of residual embryonic cells (RECs) existing at the gastroesophageal junction in normal individuals that expands and colonizes regions of the esophagus denuded by chronic reflux. These RECs form IM within days of esophageal injury, suggesting a novel mechanism of tumorigenesis.A corollary of this work is that the Barrett’s stem cell is distinct from that of the squamous epithelium and, once identified, will form the basis of new preemptive strategies for addressing Barrett’s and its related neoplasia.