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

Harada, Yoshiyuki; Masuda, Atsuhiro; Matsuura, Takanori; Nagata, Kenji; Nanno, Yoshihide; Masamune, Atsushi; Kodama, Yuzo; Hara, Eiji; Matsumoto, Tomonori

doi:https://doi.org/10.1016/j.jcmgh.2026.101808

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

Harada, Yoshiyuki; Masuda, Atsuhiro; Matsuura, Takanori et al.

Cellular and Molecular Gastroenterology and Hepatology, 2026, 20(8), 101808

アクセス数:239件（2026-11-12 04:41 集計）

固定URL: https://hdl.handle.net/11094/106747

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タイトル	Spatial Profiling Identified Senescent Cancer-Associated Fibroblasts Localized in the Border Region of Human Pancreatic Ductal Adenocarcinoma
著者	著者名 Harada, Yoshiyuki
	NRID 1000060512530 1000060512530 著者名 Masuda, Atsuhiro
	NRID 1000081000495 1000081000495 著者名 Matsuura, Takanori
	著者名 Nagata, Kenji
	NRID 1000070714666 1000070714666 著者名 Nanno, Yoshihide
	NRID 1000090312579 1000090312579 著者名 Masamune, Atsushi
	NRID 1000080378687 1000080378687 著者名 Kodama, Yuzo
	NRID 1000080263268 1000080263268 ORCID 0000-0001-7821-3960 0000-0001-7821-3960 researchmap permalink read0108962 read0108962 Scopus Author ID 7004944434 7004944434 著者名 Hara, Eiji
	NRID 1000040886610 1000040886610 ORCID 0000-0003-4483-2178 0000-0003-4483-2178 researchmap permalink tomo_matsumoto tomo_matsumoto Scopus Author ID 55628587431 55628587431 著者名 Matsumoto, Tomonori
キーワード等	Cellular Senescence
	Pancreatic Cancer
	Senescence-Associated Secretory Phenotype
	Spatial Transcriptomics
内容	Harada Y., Masuda A., Matsuura T., et al. Spatial Profiling Identified Senescent Cancer-Associated Fibroblasts Localized in the Border Region of Human Pancreatic Ductal Adenocarcinoma. Cellular and Molecular Gastroenterology and Hepatology 20, 101808 (2026); https://doi.org/10.1016/j.jcmgh.2026.101808.
抄録	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.
出版者	Elsevier Inc.
収録物名	Cellular and Molecular Gastroenterology and Hepatology
巻(号)	20(8)
ページ	101808
刊行年月	2026-06-09
言語	英語
ハンドルURL	https://hdl.handle.net/11094/106747
eISSN	2352345X
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1016/j.jcmgh.2026.101808
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Cellular and Molecular Gastroenterology and Hepatology. 2026, 20(8), p. 101808
DC.title	Spatial Profiling Identified Senescent Cancer-Associated Fibroblasts Localized in the Border Region of Human Pancreatic Ductal Adenocarcinoma
DC.creator	Harada, Yoshiyuki
	Masuda, Atsuhiro
	Matsuura, Takanori
	Nagata, Kenji
	Nanno, Yoshihide
	Masamune, Atsushi
	Kodama, Yuzo
	Hara, Eiji
	Matsumoto, Tomonori
DC.publisher	Elsevier Inc.
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2026-06-09
DC.identifier	https://doi.org/10.1016/j.jcmgh.2026.101808
DC.subject	Cellular Senescence
	Pancreatic Cancer
	Senescence-Associated Secretory Phenotype
	Spatial Transcriptomics
DC.description	Harada Y., Masuda A., Matsuura T., et al. Spatial Profiling Identified Senescent Cancer-Associated Fibroblasts Localized in the Border Region of Human Pancreatic Ductal Adenocarcinoma. Cellular and Molecular Gastroenterology and Hepatology 20, 101808 (2026); https://doi.org/10.1016/j.jcmgh.2026.101808.
DCTERMS.abstract	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.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	106747
citation_title	Spatial Profiling Identified Senescent Cancer-Associated Fibroblasts Localized in the Border Region of Human Pancreatic Ductal Adenocarcinoma
citation_author	Harada, Yoshiyuki
	Masuda, Atsuhiro
	Matsuura, Takanori
	Nagata, Kenji
	Nanno, Yoshihide
	Masamune, Atsushi
	Kodama, Yuzo
	Hara, Eiji
	Matsumoto, Tomonori
citation_publisher	Elsevier Inc.
citation_language	英語
citation_date	2026-06-09
citation_journal_title	Cellular and Molecular Gastroenterology and Hepatology
citation_volume	20
citation_issue	8
citation_firstpage	101808
citation_doi	https://doi.org/10.1016/j.jcmgh.2026.101808
citation_public_url	https://hdl.handle.net/11094/106747

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

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