Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
Int J Mol Sci. 2022 May 11;23(10):5377. doi: 10.3390/ijms23105377.
In 2020, gastric cancer was the fourth leading cause of cancer deaths globally. About 90% of gastric cancers are sporadic and the vast majority are correlated with infection; whereas familial clustering is observed in about 10% of cases. Gastric cancer is now considered to be a disease originating from dysregulated self-renewal of the gastric glands in the setting of an inflammatory environment. The human stomach contains two types of gastric units, which show bi-directional self-renewal from a complex variety of stem cells. This review focuses on recent progress concerning the characterization of the different stem cell populations and the mainly mesenchymal signals triggering their stepwise differentiation as well as the genesis of pre-cancerous lesions and carcinogenesis. Furthermore, a model is presented (Lectin-triggered Receptor Blocking Hypothesis) explaining the role of the lectin TFF1 as an antral tumor suppressor possibly regulating Lgr5 antral stem cells in a paracrine or maybe autocrine fashion, with neighboring antral gland cells having a role as niche cells.
在 2020 年，胃癌是全球癌症死亡的第四大主要原因。约 90%的胃癌为散发性，绝大多数与感染有关；而约 10%的病例存在家族聚集现象。目前认为胃癌是一种起源于炎症环境中胃腺失调自我更新的疾病。人类胃包含两种类型的胃单位，它们显示出从复杂多样的干细胞双向自我更新。这篇综述重点介绍了不同干细胞群体的特征以及触发其逐步分化的主要间充质信号，以及癌前病变和癌变的发生。此外，还提出了一个模型（凝集素触发受体阻断假说），解释了凝集素 TFF1 的作用，作为一种可能通过旁分泌或自分泌方式调节胃窦 Lgr5 干细胞的窦肿瘤抑制因子，邻近的胃窦腺细胞作为龛细胞发挥作用。
