Streptococcus anginosus promotes gastric inflammation, atrophy, and tumorigenesis in mice
Streptococcus anginosus (S. anginosus) was enriched in the gastric mucosa of patients with gastric cancer (GC). Here, we show that S. anginosus colonized the mouse stomach and induced acute gastritis. S. anginosus infection spontaneously induced progressive chronic gastritis, parietal cell atrophy,...
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Veröffentlicht in: | Cell 2024-02, Vol.187 (4), p.882-896.e17 |
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Sprache: | eng |
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Zusammenfassung: | Streptococcus anginosus (S. anginosus) was enriched in the gastric mucosa of patients with gastric cancer (GC). Here, we show that S. anginosus colonized the mouse stomach and induced acute gastritis. S. anginosus infection spontaneously induced progressive chronic gastritis, parietal cell atrophy, mucinous metaplasia, and dysplasia in conventional mice, and the findings were confirmed in germ-free mice. In addition, S. anginosus accelerated GC progression in carcinogen-induced gastric tumorigenesis and YTN16 GC cell allografts. Consistently, S. anginosus disrupted gastric barrier function, promoted cell proliferation, and inhibited apoptosis. Mechanistically, we identified an S. anginosus surface protein, TMPC, that interacts with Annexin A2 (ANXA2) receptor on gastric epithelial cells. Interaction of TMPC with ANXA2 mediated attachment and colonization of S. anginosus and induced mitogen-activated protein kinase (MAPK) activation. ANXA2 knockout abrogated the induction of MAPK by S. anginosus. Thus, this study reveals S. anginosus as a pathogen that promotes gastric tumorigenesis via direct interactions with gastric epithelial cells in the TMPC-ANXA2-MAPK axis.
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•S. anginosus is enriched in the gastric mucosa of patients with GC•S. anginosus induces gastritis-atrophy-metaplasia-dysplasia sequence in mice•S. anginosus promotes gastric tumorigenesis•TMPC-Annexin A2 axis mediates S. anginosus colonization and activates MAPK signaling
Gastric cancer has been usually linked to the bacterium Helicobacter pylori. Here, the authors identify Streptococcus anginosus as a pathogen that promotes gastric tumorigenesis through its surface protein TMPC binding through an Annexin-2 and MAPK signaling cascade. |
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ISSN: | 0092-8674 1097-4172 1097-4172 |
DOI: | 10.1016/j.cell.2024.01.004 |