✍🏼 Kaili Fu, Alvin Ho Kwan Cheung, Chi Chun Wong, Weixin Liu, Yunfei Zhou, Feixue Wang, Pingmei Huang, Kai Yuan, Olabisi Oluwabukola Coker,  Yasi Pan, Danyu Chen, Nga Man Lam, Mengxue Gao, Xiang Zhang, He Huang, Ka Fai To, Joseph Jao Yiu Sung, Jun Yu

🏠 Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China

📑 Cell (2024)

Abstract
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.

How the WOLF was used in this study
The WOLF Cell Sorter was employed as part of the workflow for single-cell RNA sequencing to define cell type composition within gastric tumors. After dissociation of YTN16 allograft tumors into single-cell suspensions, cells were labeled with FITC-conjugated anti-mouse CD45 and propidium iodide to distinguish live immune cells from other populations. The WOLF sorter was then used to physically separate live CD45⁺ immune cells from CD45⁻ non-immune cells, providing purified fractions for downstream single-cell transcriptomic profiling. This sorting step enabled high-resolution characterization of epithelial and immune cell subsets within the tumor microenvironment, which was essential for subsequent analyses of differential gene expression and cellular heterogeneity in the context of S. anginosus-driven gastric tumorigenesis.