Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer
Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer
复制标题
DOI：
10.1016/s0016-5085(00)70412-4
复制
发表时间：
2000-01-01
期刊：
影响因子：
29.4
通讯作者：
Fox, JG
中科院分区：
文献类型：
--
作者：
Wang, TC;Dangler, CA;Fox, JG
背景和目标：高胃泌素血症常与胃酸抑制和螺杆菌感染相关，但其在胃萎缩和胃癌进展中的作用尚未明确。研究方法：在胰岛素-胃泌素（INS-GAS）转基因小鼠中研究了高胃泌素血症的影响以及与猫螺杆菌感染的可能协同作用。结果如下：INS-GAS小鼠最初表现为轻度高胃泌素血症，最大胃酸分泌增加，壁细胞数量增加，但后来进展为壁细胞数量减少和低氯血症。胃萎缩的发生与生长因子、肝素结合表皮生长因子和转化生长因子的表达增加有关。在20个月大时，INS-GAS小鼠没有表现出肠嗜铬样细胞数量增加的证据，而是表现出胃化生、异型增生、原位癌和胃癌伴血管浸润。在8只>20月龄的INS-GAS小鼠中的6只中观察到浸润性胃癌。INS-GAS小鼠的猫螺杆菌感染导致粘膜内癌（85%）、粘膜下浸润（54%）和血管内浸润（46%）的加速（小于或等于8个月）发展（P小于或等于0.05）。结论：这些发现支持了一个意想不到的结论，即小鼠慢性高胃泌素血症可与螺杆菌感染协同作用，并最终导致壁细胞丢失和进展为胃癌。
Background & Aims: Hypergastrinemia occurs frequently in association with acid suppression and Helicobacter infection, but its role in the progression to gastric atrophy and gastric cancer has not been well defined. Methods: The effects of hypergastrinemia, and possible synergy with Helicobacter felis infection, were investigated in insulin-gastrin (INS-GAS) transgenic mice. Results: INS-GAS mice initially showed mild hypergastrinemia, increased maximal gastric acid secretion, and increased parietal cell number but later progressed to decreased parietal cell number and hypochlorhydria, Development of gastric atrophy was associated with increased expression of growth factors, heparin-binding epidermal growth factor and transforming growth factor or. At 20 months of age, INS-GAS mice showed no evidence of increased enterochromaffin-like cell number, but instead exhibited gastric metaplasia, dysplasia, carcinoma in situ, and gastric cancer with vascular invasion. Invasive gastric carcinoma was observed in 6 of 8 INS-GAS mice that were >20 months old. Helicobacter felis infection of INS-GAS mice led to accelerated (less than or equal to 8 mo) development of intramucosal carcinoma (85%), with submucosal invasion (54%) and intravascular invasion (46%; P less than or equal to 0.05). Conclusions: These findings support the unexpected conclusion that chronic hypergastrinemia in mice can synergize with Helicobacter infection and contribute to eventual parietal cell loss and progression to gastric cancer.