Department of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, 1130 St. Nicholas Avenue, New York, NY, 10032, USA.
Department of Internal Medicine, Munich Technical University, Ismaninger Strasse 22, 81675, Munich, Germany.
Dig Dis Sci. 2018 Aug;63(8):2013-2021. doi: 10.1007/s10620-018-5152-y.
The incidence of esophageal adenocarcinoma (EAC) and its precursor lesion Barrett's esophagus (BE) has been increasing steadily in the western world in recent decades. Understanding the cellular origins of BE and the conditions responsible for their malignant transformation would greatly facilitate risk assessment and identification of patients at risk of progression, but this topic remains a source of debate. Here, we review recent findings that have provided support for the gastroesophageal junction (GEJ) as the main source of stem cells that give rise to BE and EAC. These include both gastric cardia cells and transitional basal cells. Furthermore, we discuss the role of chronic injury and inflammation in a tumor microenvironment as a major factor in promoting stem cell expansion and proliferation as well as transformation of the GEJ-derived stem cells and progression to EAC. We conclude that there exists a large amount of empirical support for the GEJ as the likely source of BE stem cells. While BE seems to resemble a successful adaptation to esophageal damage, carcinogenesis appears as a consequence of natural selection at the level of GEJ stem cells, and later glands, that expand into the esophagus wherein the local ecology creates the selective landscape for cancer progression.
食管腺癌（EAC）及其前体病变巴雷特食管（BE）的发病率在近几十年来在西方世界稳步上升。了解 BE 的细胞起源以及导致其恶性转化的条件将极大地促进风险评估和识别进展风险的患者，但这一主题仍然存在争议。在这里，我们回顾了最近的发现，这些发现为胃食管交界处（GEJ）作为产生 BE 和 EAC 的干细胞的主要来源提供了支持。这些包括胃贲门细胞和过渡基底细胞。此外，我们讨论了慢性损伤和炎症在肿瘤微环境中的作用，作为促进 GEJ 衍生干细胞扩张和增殖以及向 EAC 转化的主要因素。我们得出结论，有大量的经验证据支持 GEJ 作为 BE 干细胞的可能来源。虽然 BE 似乎类似于对食管损伤的成功适应，但癌变似乎是 GEJ 干细胞水平自然选择的结果，随后是腺体扩张进入食管，局部生态创造了癌症进展的选择景观。
