ArticleCellular and molecular gastroenterology and hepatology2026
Spatial Profiling Identified Senescent Cancer-Associated Fibroblasts Localized in the Border Region of Human Pancreatic Ductal Adenocarcinoma.
Article in Cellular and molecular gastroenterology and hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND &
aimsPancreatic ductal adenocarcinoma is a highly aggressive malignancy characterized by a fibroblast-rich tumor microenvironment. Cancer-associated fibroblasts closely interact with tumor cells and play a pivotal role in cancer pathogenesis. Single-cell analyses have identified distinct cancer-associated fibroblast subsets that exert either tumor-promoting or tumor-suppressive effects in pancreatic ductal adenocarcinoma. Senescent cancer-associated fibroblasts have recently been linked to poor prognosis through their senescence-associated secretory phenotype. However, the dynamics of senescent cancer-associated fibroblast induction and their spatial distribution in pancreatic ductal adenocarcinoma remain largely unclear. This study aimed to investigate the heterogeneity and spatial organization of cancer-associated fibroblasts in pancreatic ductal adenocarcinoma, with a specific focus on the induction and localization of senescent cancer-associated fibroblasts.
methodsWe performed immunostaining and spatial transcriptomic analyses covering unbiased regions of tumor architecture to map cancer-associated fibroblast subpopulations and characterize senescent cancer-associated fibroblast induction and localization.
resultsSenescent cancer-associated fibroblasts were found to accumulate preferentially at the gross tumor edge, and their abundance was associated with poor patient prognosis. Chemotherapy further promoted senescence in myofibroblastic cancer-associated fibroblasts within the tumor core, resulting in an increased population of senescent cancer-associated fibroblasts. Spatial transcriptomic profiling identified gene signatures specific to senescent cancer-associated fibroblasts and revealed their distinct interactions with neighboring cells. Notably, senescent cancer-associated fibroblasts exhibited enhanced transforming growth factor-β signaling activity and upregulation of downstream genes, such as CCN2 and PLAU, which may contribute to tumor proliferation and invasion.
conclusionsThis study reveals that senescent cancer-associated fibroblasts preferentially localize near the gross tumor edge and could impact tumor progression through their senescence-associated secretory phenotype. These findings highlight the spatial plasticity of pancreatic cancer-associated fibroblasts and underscore the pathological significance of senescent cancer-associated fibroblasts in human pancreatic ductal adenocarcinoma.
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