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Abstract
(1) Background: Persistent Helicobacter pylori infection is the most important risk factor for gastric cancer. The urokinase receptor (uPAR) is upregulated in lesions harboring cancer invasion and inflammation. Circumstantial evidence tends to correlate H. pylori colonization with increased uPAR expression in the human gastric epithelium, but a direct causative link has not yet been established in vivo; (2) Methods: In a mouse model of H. pylori-induced gastritis, we investigated the temporal emergence of uPAR protein expression in the gastric mucosa in response to H. pylori (SS1 strain) infection; (3) Results: We observed intense uPAR immunoreactivity in foveolar epithelial cells of the gastric corpus due to de novo synthesis, compared to non-infected animals. This uPAR induction represents a very early response, but it increases progressively over time as do infiltrating immune cells. Eradication of H. pylori infection by antimicrobial therapy causes a regression of uPAR expression to its physiological baseline levels. Suppression of the inflammatory response by prostaglandin E2 treatment attenuates uPAR expression. Notwithstanding this relationship, H. pylori does induce uPAR expression in vitro in co-cultures with gastric cancer cell lines; (4) Conclusions: We showed that persistent H. pylori colonization is a necessary event for the emergence of a relatively high uPAR protein expression in murine gastric epithelial cells.
Highlights
Gastric cancer is the final clinical endpoint of a stepwise process in which Helicobacter pylori infection plays a central role [1,2]
Circumstantial evidence suggests that this bacterial infection may be involved in the induction of components of the plasminogen activation system in the gastric mucosa, in particular uPAR [27,29]
This phenomenon may be relevant for the development of gastric pathologies, given the central role of uPAR in plasminogen-mediated extracellular matrix remodeling [47,48,49], vitronectin-dependent cell adhesion and migration [14,15], and its upregulation in gastric cancer and associated prognostic impact [11,29,49]
Summary
Gastric cancer is the final clinical endpoint of a stepwise process in which Helicobacter pylori infection plays a central role [1,2]. Other gastric pathologies associated with H. pylori infection include peptic ulcer disease and mucosa-associated lymphoid tissue (MALT) lymphomas [3]. This bacterial infection has been inversely associated with a range of extra-gastric systemic manifestations, including asthma and allergies [4,5]. The infection is usually established early in life and persists lifelong in the absence of treatment. This leads to a sustained chronic inflammation characterized by infiltration of inflammatory cells in the gastric mucosa and expression of inflammatory mediators by immune and epithelial cells [6,7]. How H. pylori and its virulence factors interfere with the physiological processes as well as the biological mechanisms determining the final outcome remain largely unknown
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