Department of Physiology, the Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Kraków, Poland.
Cancer Metastasis Rev. 2023 Dec;42(4):1219-1256. doi: 10.1007/s10555-023-10122-1. Epub 2023 Jul 17.
The discovery of Helicobacter pylori (Hp) infection of gastric mucosa leading to active chronic gastritis, gastroduodenal ulcers, and MALT lymphoma laid the groundwork for understanding of the general relationship between chronic infection, inflammation, and cancer. Nevertheless, this sequence of events is still far from full understanding with new players and mediators being constantly identified. Originally, the Hp virulence factors affecting mainly gastric epithelium were proposed to contribute considerably to gastric inflammation, ulceration, and cancer. Furthermore, it has been shown that Hp possesses the ability to penetrate the mucus layer and directly interact with stroma components including fibroblasts and myofibroblasts. These cells, which are the source of biophysical and biochemical signals providing the proper balance between cell proliferation and differentiation within gastric epithelial stem cell compartment, when exposed to Hp, can convert into cancer-associated fibroblast (CAF) phenotype. The crosstalk between fibroblasts and myofibroblasts with gastric epithelial cells including stem/progenitor cell niche involves several pathways mediated by non-coding RNAs, Wnt, BMP, TGF-β, and Notch signaling ligands. The current review concentrates on the consequences of Hp-induced increase in gastric fibroblast and myofibroblast number, and their activation towards CAFs with the emphasis to the altered communication between mesenchymal and epithelial cell compartment, which may lead to inflammation, epithelial stem cell overproliferation, disturbed differentiation, and gradual gastric cancer development. Thus, Hp-activated fibroblasts may constitute the target for anti-cancer treatment and, importantly, for the pharmacotherapies diminishing their activation particularly at the early stages of Hp infection.
幽门螺杆菌（Hp）感染胃黏膜导致活动性慢性胃炎、胃十二指肠溃疡和黏膜相关淋巴组织（MALT）淋巴瘤的发现，为理解慢性感染、炎症和癌症之间的一般关系奠定了基础。然而，这一事件序列仍然远未完全被理解，新的参与者和介质不断被发现。最初，被认为主要影响胃上皮的 Hp 毒力因子被认为对胃炎症、溃疡和癌症有相当大的贡献。此外，已经表明 Hp 具有穿透黏液层并直接与包括成纤维细胞和肌成纤维细胞在内的基质成分相互作用的能力。这些细胞是生物物理和生化信号的来源，为胃上皮干细胞龛中的细胞增殖和分化之间提供适当的平衡，当暴露于 Hp 时，它们可以转化为癌相关成纤维细胞（CAF）表型。成纤维细胞和肌成纤维细胞与包括干细胞/祖细胞龛在内的胃上皮细胞之间的串扰涉及几种非编码 RNA、Wnt、BMP、TGF-β和 Notch 信号配体介导的途径。目前的综述集中在 Hp 诱导胃成纤维细胞和肌成纤维细胞数量增加及其向 CAFs 激活的后果上，并强调了间质和上皮细胞龛之间改变的通讯，这可能导致炎症、上皮干细胞过度增殖、分化紊乱和逐渐发展为胃癌。因此，Hp 激活的成纤维细胞可能成为抗癌治疗的靶点，重要的是，在 Hp 感染的早期阶段，针对减少其激活的药物治疗。
