Division of Microbiology, Department of Biosciences and Medical Biology, Paris Lodron University of Salzburg, Hellbrunner Strasse 34, 5020 Salzburg, Austria.
Cancer Cluster Salzburg and Allergy Cancer BioNano Research Centre, University of Salzburg, Hellbrunner Strasse 34, 5020 Salzburg, Austria.
Int J Mol Sci. 2022 Feb 22;23(5):2419. doi: 10.3390/ijms23052419.
Gastric cancer is a leading cause of cancer-related death, and a large proportion of cases are inseparably linked to infections with the bacterial pathogen and type I carcinogen . The development of gastric cancer follows a cascade of transformative tissue events in an inflammatory environment. Proteases of host origin as well as -derived proteases contribute to disease progression at every stage, from chronic gastritis to gastric cancer. In the present article, we discuss the importance of (metallo-)proteases in colonization, epithelial inflammation, and barrier disruption in tissue transformation, deregulation of cell proliferation and cell death, as well as tumor metastasis and neoangiogenesis. Proteases of the matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase domain-containing protein (ADAM) families, caspases, calpain, and the proteases HtrA, Hp1012, and Hp0169 cleave substrates including extracellular matrix molecules, chemokines, and cytokines, as well as their cognate receptors, and thus shape the pathogenic microenvironment. This review aims to summarize the current understanding of how proteases contribute to disease progression in the gastric compartment.
胃癌是癌症相关死亡的主要原因，很大一部分病例与细菌病原体和 I 型致癌物的感染密不可分。胃癌的发生遵循炎症环境中一系列转化性组织事件的级联反应。宿主来源的蛋白酶以及衍生的蛋白酶在疾病的每一个阶段都起到了促进作用，从慢性胃炎到胃癌。在本文中，我们讨论了（金属）蛋白酶在定植、上皮炎症和组织转化中的屏障破坏、细胞增殖和细胞死亡的失调以及肿瘤转移和新生血管形成中的重要性。基质金属蛋白酶 (MMP) 和解整合素金属蛋白酶域蛋白 (ADAM) 家族、半胱天冬酶、钙蛋白酶以及蛋白酶 HtrA、Hp1012 和 Hp0169 的蛋白酶可切割细胞外基质分子、趋化因子和细胞因子及其同源受体等底物，从而塑造致病微环境。本综述旨在总结目前对蛋白酶如何促进胃区疾病进展的认识。
