ArticleMatrix biology plus2022
Matrix stiffness mediates pancreatic cancer chemoresistance through induction of exosome hypersecretion in a cancer associated fibroblasts-tumor organoid biomimetic model.
Article in Matrix biology plus, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- Small Extracellular Vesicle-Derived Nidogen 1 Promotes HCC Carcinogenesis via Transglutaminase 3-Mediated YAP/TAZ Signalling.Journal of extracellular vesicles · 2026Article
- Mechanobiology of the tumor microenvironment: a review of therapeutic interactions and in vitro elasticity measurement techniques.Journal of biomedical science · 2026Review
- The synergistic applications of organoids and exosomes in disease modeling and disease treatment.Molecular biology reports · 2026Review
- Tumor Organoid and Microenvironment Cocultures: Implications for Basic and Translational Cancer Research.MedComm · 2026Review
- Methods and applications of patient-derived organoid models for immune microenvironment and immunotherapy research in multiple cancer types.Experimental hematology & oncology · 2026Review
- Targeting Tumor-Associated Macrophages to Reshape the Immuno-Mechanical Landscape: Molecular Mechanisms and Therapeutic Strategies.International journal of biological sciences · 2026Review
- Cancer-Associated Fibroblast-Targeted Nanomedicine in Solid Tumor Therapy: From Mechanisms of Therapeutic Resistance to Precision Stromal Modulation.International journal of nanomedicine · 2026Review
- Tumor peripheral stiffness modulates lenvatinib resistance in HCC preclinical models by regulating FIS1-dependent mitophagy.JHEP reports : innovation in hepatology · 2025Article
- Mechanical regulation of extracellular vesicle activity during tumour progression.Nature biomedical engineering · 2025Review
- Extracellular Matrix Signaling Cues: Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- The 3D Language of Cancer: Communication via Extracellular Vesicles from Tumor Spheroids and Organoids.International journal of molecular sciences · 2025Review
- Bioprinted Patient-Derived Organoid Arrays Capture Intrinsic and Extrinsic Tumor Features for Advanced Personalized Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Melanoma-derived extracellular vesicles transfer proangiogenic factors.Oncology research · 2025Review
- Differential Effects of Confinement on the Dynamics of Normal and Tumor-Derived Pancreatic Ductal Organoids.ACS applied bio materials · 2024Article
- Hydrogel models of pancreatic adenocarcinoma to study cell mechanosensing.Biophysical reviews · 2024Review
- Altered Mechanobiology of PDAC Cells with Acquired Chemoresistance to Gemcitabine and Paclitaxel.Cancers · 2024Article
- Exploiting Matrix Stiffness to Overcome Drug Resistance.ACS biomaterials science & engineering · 2024Review
- Engineered matrices reveal stiffness-mediated chemoresistance in patient-derived pancreatic cancer organoids.Nature materials · 2024Article
- Drug-Resistance Biomarkers in Patient-Derived Colorectal Cancer Organoid and Fibroblast Co-Culture System.Current issues in molecular biology · 2024Article
- Biophysical perspectives to understanding cancer-associated fibroblasts.APL bioengineering · 2024Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In pancreatic ductal adenocarcinoma (PDAC), the abundant stromal cells which comprise the tumor microenvironment constitute more than 90% of the primary tumor bulk. Moreover, this desmoplastic environment has been found to be three times stiffer than normal pancreas tissue. Despite the importance of studying the desmoplastic environment of PDAC, there is still a lack of models designed to adequately recapitulate this complex stiff microenvironment, a critical hallmark of the disease that has been shown to induce chemoresistance. Here, we present a bio-mimetic, 3-dimensional co-culture system that integrates tumor organoids and host-matching stromal cancer associated-fibroblasts (CAFs) that recapitulates the complex, fibrotic matrix of PDAC using advanced biomaterials. With this model, we show that matrix-activated CAFs are able to "re-engineer" the fibrotic environment into a significantly stiffer environment through lysyl-oxidase dependent crosslinking. Moreover, we show that culture of CAFs in this model leads to an increase of exosomes; extracellular vesicles known to promote chemoresistance. Finally, using previously identified exosome inhibitors, climbazole and imipramine, we demonstrate how abrogation of exosome hypersecretion can reduce matrix stiffness-induced chemoresistance. These data highlight the importance of the development of new models that recapitulate not only the cellular composition found in PDAC tumors, but also the biophysical stresses, like stiffness, that the cells are exposed to in order to identify therapies that can overcome this critical feature which can contribute to the chemoresistance observed in patients. We believe that the 3D bio-mimetic model we have developed will be a valuable tool for the development, testing, and optimization of "mechano-medicines" designed to target the biophysical forces that lead to tumor growth and chemoresistance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.