Spatial Profiling Identified Senescent Cancer-Associated Fibroblasts Localized in the Border Region of Human Pancreatic Ductal Adenocarcinoma

Sep 22, 2026

Upload by Aran

Human pancreatic ductal adenocarcinoma features abundant cancer-associated fibroblasts (CAFs) whose spatial behavior and senescence-driven roles are incompletely defined. This study uses immunostaining and spatial transcriptomics to map fibroblast subpopulations across tumor regions and examines senescent CAF induction under chemotherapy. Senescent CAFs coexpress myofibroblastic and inflammatory markers, preferentially localize at the gross tumor edge, associate with poor prognosis, and expand after chemotherapy, suggesting functional impact via senescence-associated secretory phenotype.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Summary

What You Need to Know

Background

Impact

Future Directions

Background & Aims

Methods

Results

Conclusions

ORIGINAL RESEARCH Spatial Profiling Identified Senescent Cancer-Associated Fibroblasts Localized in the Border Region of Human Pancreatic Ductal Adenocarcinoma Yoshiyuki Harada, 1 ,2 ,3 Atsuhiro Masuda,2 Takanori Matsuura, 1 ,2 Kenji Nagata, 1 ,2 ,3 Yoshihide Nanno,4 Atsushi Masamune,5 Yuzo Kodama,2 Eiji Hara, 1 ,6 and Tomonori Matsumoto 1 ,3 1Department of Molecular Biology, Research Institute for Microbial Diseases, The University of Osaka, Osaka, Japan; 2Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan; 3Laboratory of Ploidy Pathology, Graduate School of Frontier Biosciences, The University of Osaka, Osaka, Japan; 4Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Japan; 5Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan; and 6Laboratory of Aging Biology, Immunology Frontier Research Center, The University of Osaka, Osaka, Japan | Spatial profiling identified senescent CAFs localized in the border region of human PDAC | | --- | |
Methods Outcome
| SUMMARY In human pancreatic ductal adenocarcinoma, senescent cancer-associated fibroblasts coexpress myofibroblastic and inflammatory cancer-associated fibroblast markers and preferentially localize at the gross tumor edge. Chemotherapy further induces this population, and senescent cancer-associated fibroblasts could influence disease progression through their senescence-associated secretory phenotype. WHAT YOU NEED TO KNOW Background: Pancreatic ductal adenocarcinoma contains abundant cancer-associated fibroblasts with diverse functions. Senescent cancer-associated fibroblasts, via asenescence-associated secretory phenotype, predict poor outcomes, yet their spatial dynamics remain undefined. Impact: Immunostaining and spatial transcriptomics mapped fibroblast subpopulations across tumor regions. Senescent cancer-associated fibroblasts concentrate at the gross tumor edge, associate with poor survival, and expand after chemotherapy in myofibroblastic fibroblasts. Future Directions: Eliminating senescent cancerassociated fibroblasts or suppressing their senescenceassociated secretory phenotype may limit invasion. Transforming growth factor-ß–axis molecules such as CCN2 and PLAU could serve as biomarkers and therapeutic targets to modulate stromal remodeling. 2 Harada et al Cellular and Molecular Gastroenterology and Hepatology Vol. 20, Iss. 8 BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma is a highly aggressive malignancy characterized by a fibroblastrich 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 ofsenescent cancer-associated fibroblasts. METHODS: We performed immunostaining and spatial transcriptomic analyses covering unbiased regions of tumor architecture to map cancer-associated fibroblast subpopulationsand 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 prom

FAQs

What is the central finding about senescent cancer-associated fibroblasts in PDAC?

Senescent cancer-associated fibroblasts preferentially accumulate at the gross tumor edge in human pancreatic ductal adenocarcinoma. Their abundance is linked to poor patient prognosis.

How were senescent CAFs identified and localized in this study?

The study combined immunostaining with spatial transcriptomic analyses across unbiased regions of tumor architecture. This mapped fibroblast subpopulations and characterized senescent CAF induction and localization.

What effect does chemotherapy have on senescent CAF populations?

Chemotherapy further promotes senescence, increasing senescent cancer-associated fibroblasts by inducing senescence in myofibroblastic cancer-associated fibroblasts within the tumor core.

Sep 22, 2026

Upload by Aran