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Updated: May 14, 2026
Isolation of Normal and Cancer-associated Fibroblasts from Fresh Tissues by Fluorescence Activated Cell Sorting (FACS)
Published on: January 14, 2013
Spatial Profiling Identified Senescent Cancer-Associated Fibroblasts Localized in the Border Region of Human
Yoshiyuki Harada1, Atsuhiro Masuda2, Takanori Matsuura3
1Department of Molecular Biology, Research Institute for Microbial Diseases, The University of Osaka, Osaka, Japan; Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan; Laboratory of Ploidy Pathology, Graduate School of Frontier Biosciences, The University of Osaka, Osaka, Japan.
Background & Aims:
Pancreatic 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.
Methods:
We 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.
Results:
Senescent 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.
Conclusions:
This 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.
