Helicobacter pylori plays a key role in gastric adenocarcinoma induced by spasmolytic polypeptide-expressing metaplasia

Figure 1 Alteration of glandular cells during spasmolytic polypeptide-expressing metaplasia malignant progression due to Heliobacter pylori infection. Under the influences of chronic inflammation, CD44 variant 9, and whey acidic protein 4-disulfide core domain protein 2 produced by spasmolytic polypeptide-expressing metaplasia (SPEM) malignant cells, M1 and M2 polarization is induced in local macrophages, after which M1 polarized macrophages will secrete interferon-γ, which is one of the important inflammatory factors that aggravate local inflammation. M2 polarization causes macrophages to secrete large amounts of interleukin-33, which aggravates the transdifferentiation of mature master cells and promotes the malignant progression of SPEM. Citation: Created with BioRender.com. (Supplementary material). SPEM: Spasmolytic polypeptide-expressing metaplasia; IL: Interleukin; WFDC: Whey acidic protein 4-disulfide core domain protein 2; CD44v9: CD44 variant isoform 9.

Figure 2 Influence of immune cells and cytokines on spasmolytic polypeptide-expressing metaplasia development. Parietal cells of fundic glands are gradually lost and mature chief cells transdifferentiate into spasmolytic polypeptide-expressing metaplasia (SPEM) in gland bases due to the chronic inflammation caused by Helicobacter pylori infection. In earlier stages, trefoil factor (TFF) 2+/MIST1+ and TFF2+/MIST1- SPEM cells appear at the bases of the same glands. As the inflammation progresses, MIST1 and TFF2 double-positive SPEM cells are gradually replaced by TFF2+/MIST1- cells, in which high expression of CD44V9 and whey acidic protein 4-disulfide core domain protein 2 and macrophage M2 polarization play important roles leading glands to intestinal metaplasia characterized by goblet and Paneth cells. Citation: Created with BioRender.com. (Supplementary material). IFN: Interferon; IL: Interleukin; WFDC: Whey acidic protein 4-disulfide core domain protein 2; CD44v9: CD44 variant isoform 9.