Apposition of Fibroblasts With Metaplastic Gastric Cells Promotes Dysplastic Transition.
BACKGROUND & AIMS: Elements of field cancerization, including atrophic gastritis, metaplasia, and dysplasia, promote gastric cancer development in association with chronic inflammation. However, it remains unclear how stroma changes during carcinogenesis and how the stroma contributes to progression of gastric preneoplasia. Here we investigated heterogeneity of fibroblasts, one of the most important elements in the stroma, and their roles in neoplastic transformation of metaplasia.
METHODS: We used single-cell transcriptomics to evaluate the cellular heterogeneity of mucosal cells from patients with gastric cancer. Tissue sections from the same cohort and tissue microarrays were used to identify the geographical distribution of distinct fibroblast subsets. We further evaluated the role of fibroblasts from pathologic mucosa in dysplastic progression of metaplastic cells using patient-derived metaplastic gastroids and fibroblasts.
RESULTS: We identified 4 subsets of fibroblasts within stromal cells defined by the differential expression of PDGFRA, FBLN2, ACTA2, or PDGFRB. Each subset was distributed distinctively throughout stomach tissues with different proportions at each pathologic stage. The PDGFRα
CONCLUSIONS: These findings indicate that fibroblast associations with metaplastic epithelial cells can facilitate direct transition of metaplastic spasmolytic polypeptide-expressing metaplasia cell lineages into dysplastic lineages.
Institute for Systems Biology
Lee, Su-Hyung; Contreras Panta, Ela W; Gibbs, David; Won, Yoonkyung; Min, Jimin; Zhang, Changqing; Roland, Joseph T; Hong, Se-Hoon; Sohn, Yoojin; Krystofiak, Evan; Jang, Bogun; Ferri, Lorenzo; Sangwan, Veena; Ragoussis, Jiannis; Camilleri-Broët, Sophie; Caruso, Joseph; Chen-Tanyolac, Chira; Strasser, Michael; Gascard, Philippe; Tlsty, Thea D; Huang, Sui; Choi, Eunyoung; and Goldenring, James R, "Apposition of Fibroblasts With Metaplastic Gastric Cells Promotes Dysplastic Transition." (2023). Articles, Abstracts, and Reports. 7348.