ArticleThe Journal of pathology2022
Periostin- and podoplanin-positive cancer-associated fibroblast subtypes cooperate to shape the inflamed tumor microenvironment in aggressive pancreatic adenocarcinoma.
Article in The Journal of pathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- The extracellular matrix in cancer-associated fibrosis: molecular mechanisms and clinical relevance.JCI insight · 2026Review
- Distinct Malignant Cell States and Myeloid Glutamate Signaling Associated with Aggressive Pancreatic Neuroendocrine Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Radiation-Induced Alterations in Cancer-Associated Fibroblasts: Drivers of Tumor Radioresistance and Therapeutic Targets.Biomolecules · 2026Review
- A tumor microenvironment integrated (TMI) staging system for pancreatic ductal adenocarcinoma based on cancer-associated fibroblast and molecular consensus signatures.Discover oncology · 2026Article
- Cancer-Associated Fibroblasts Functions as Multifunctional Architects of the Tumor Stroma and Represent Emerging Therapeutic Vulnerabilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- ProAgio, a Novel Integrin αvβ3 Targeted Cytotoxin, Suppresses Tumor Growth and Reprograms the PDAC Microenvironment.bioRxiv : the preprint server for biology · 2026Article
- Spatial Profiling Identified Senescent Cancer-Associated Fibroblasts Localized in the Border Region of Human Pancreatic Ductal Adenocarcinoma.Cellular and molecular gastroenterology and hepatology · 2026Article
- Cancer-Associated Fibroblasts: Clinical Applications in Imaging and Therapy.Tomography (Ann Arbor, Mich.) · 2025Review
- Unraveling the YAP1-TGFβ1 axis: a key driver of androgen receptor loss in prostate cancer-associated fibroblasts.Journal of experimental & clinical cancer research : CR · 2025Article
- Review
- Cancer-associated fibroblast marker signatures and stromal composition in usual interstitial pneumonia-associated lung adenocarcinoma: an analysis using a proteomic-immunohistochemical approach.Virchows Archiv : an international journal of pathology · 2025Article
- Article
- Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma.Scientific reports · 2025Article
- Advances in nanotechnology for targeting cancer-associated fibroblasts: A review of multi-strategy drug delivery and preclinical insights.APL bioengineering · 2025Review
- Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects.Journal of biomedical science · 2025Review
- A Role for Periostin Pathological Variants and Their Interaction with HSP70-1a in Promoting Pancreatic Cancer Progression and Chemoresistance.International journal of molecular sciences · 2024Article
- Cancer-associated fibroblasts: a versatile mediator in tumor progression, metastasis, and targeted therapy.Cancer metastasis reviews · 2024Review
- Expression of Periostin Alternative Splicing Variants in Normal Tissue and Breast Cancer.Biomolecules · 2024Article
- The role of cancer-associated fibroblasts and exosomal miRNAs-mediated intercellular communication in the tumor microenvironment and the biology of carcinogenesis: a systematic review.Cell death discovery · 2024Review
- Tumor battlefield within inflamed, excluded or desert immune phenotypes: the mechanisms and strategies.Experimental hematology & oncology · 2024Review
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Cancer-associated fibroblasts (CAFs) are orchestrators of the pancreatic ductal adenocarcinoma (PDAC) microenvironment. Previously we described four CAF subtypes with specific molecular and functional features. Here, we have refined our CAF subtype signatures using RNAseq and immunostaining with the goal of defining bioinformatically the phenotypic stromal and tumor epithelial states associated with CAF diversity. We used primary CAF cultures grown from patient PDAC tumors, human data sets (in-house and public, including single-cell analyses), genetically engineered mouse PDAC tissues, and patient-derived xenografts (PDX) grown in mice. We found that CAF subtype RNAseq signatures correlated with immunostaining. Tumors rich in periostin-positive CAFs were significantly associated with shorter overall survival of patients. Periostin-positive CAFs were characterized by high proliferation and protein synthesis rates and low α-smooth muscle actin expression and were found in peri-/pre-tumoral areas. They were associated with highly cellular tumors and with macrophage infiltrates. Podoplanin-positive CAFs were associated with immune-related signatures and recruitment of dendritic cells. Importantly, we showed that the combination of periostin-positive CAFs and podoplanin-positive CAFs was associated with specific tumor microenvironment features in terms of stromal abundance and immune cell infiltrates. Podoplanin-positive CAFs identified an inflammatory CAF (iCAF)-like subset, whereas periostin-positive CAFs were not correlated with the published myofibroblastic CAF (myCAF)/iCAF classification. Taken together, these results suggest that a periostin-positive CAF is an early, activated CAF, associated with aggressive tumors, whereas a podoplanin-positive CAF is associated with an immune-related phenotype. These two subpopulations cooperate to define specific tumor microenvironment and patient prognosis and are of putative interest for future therapeutic stratification of patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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