ArticleThe American journal of pathology2009
Organotypic culture model of pancreatic cancer demonstrates that stromal cells modulate E-cadherin, beta-catenin, and Ezrin expression in tumor cells.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 130 citations in OpenAlex.
- Rapid autofluorescence based 3D optical imaging of the pancreatic cancer milieu at mesoscopic scale - stain-free volumetric segmentation.Scientific reports · 2026Article
- Chronic cadmium exposure promotes TRPM7-dependent acquisition of a myofibroblast-like phenotype in pancreatic stellate cells.Cell biology and toxicology · 2026Article
- ZEB1, a novel junctional adhesion molecule A regulator, impacts sensitivity of pancreatic cancer-associated fibroblasts to reovirus.Molecular therapy. Oncology · 2025Article
- Mapping Tumor-Stroma-ECM Interactions in Spatially Advanced 3D Models of Pancreatic Cancer.ACS applied materials & interfaces · 2025Article
- A promising breakthrough in pancreatic cancer research: The potential of spheroids as 3D models.BioImpacts : BI · 2025Review
- In vitro and ex vivo evaluation of preclinical models for FAP-targeted theranostics: differences and relevance for radiotracer evaluation.EJNMMI research · 2024Article
- TGF-β Signaling Loop in Pancreatic Ductal Adenocarcinoma Activates Fibroblasts and Increases Tumor Cell Aggressiveness.Cancers · 2024Article
- Preclinical evaluation of the gorilla-derived HAdV-B AdV-lumc007 oncolytic adenovirus 'GoraVir' for the treatment of pancreatic ductal adenocarcinoma.Molecular oncology · 2024Article
- Pancreatic cancer-associated fibroblasts modulate macrophage differentiation via sialic acid-Siglec interactions.Communications biology · 2024Article
- The context-dependent role of the NaPflugers Archiv : European journal of physiology · 2023Article
- Article
- A Step-by-Step Methodological Guide for Developing Zonal Multicellular Scaffold-Based Pancreatic Cancer Models.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Gastrointestinal cancer-associated fibroblasts expressing Junctional Adhesion Molecule-A are amenable to infection by oncolytic reovirus.Cancer gene therapy · 2022Article
- Review
- A Case Report on Longitudinal Collection of Tumour Biopsies for Gene Expression-Based Tumour Microenvironment Analysis from Pancreatic Cancer Patients Treated with Endoscopic Ultrasound Guided Radiofrequency Ablation.Current oncology (Toronto, Ont.) · 2022Article
- Article
- MHC class II molecules on pancreatic cancer cells indicate a potential for neo-antigen-based immunotherapy.Oncoimmunology · 2022Article
- A Novel Pancreatic Cancer Mini-tumor Model to Study Desmoplasia and Myofibroblastic Cancer-Associated Fibroblast Differentiation.Gastro hep advances · 2022Review
- In 2D and 3D Cell Culture Models, Effects of Endothelial Cells on E-cadherin / β-catenin Expression Levels and Spheroid Sizes in Ishikawa Cells.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Pancreatic cancer is characterized by an intense stromal reaction. Reproducible three-dimensional in vitro systems for exploring interactions of the stroma with pancreatic cancer cells have not previously been available, prompting us to develop such a model. Cancer cells were grown on collagen/Matrigel and embedded with or without stromal cells (hTERT-immortalized human PS-1 stellate cells or MRC-5 fibroblasts) for 7 days. Proliferation and apoptosis, as well as important cell-cell adhesion and cytoskeleton-regulating proteins, were studied. PS-1 cells were confirmed as stellate based on the expression of key cytoskeletal proteins and lipid vesicles. Capan-1, and to a lesser extent PaCa-3, cells differentiated into luminal structures, exhibiting a central apoptotic core with a proliferating peripheral rim and an apico-basal polarity. Presence of either stromal cell type translocated Ezrin from apical (when stromal cells were absent) to basal aspects of cancer cells, where it was associated with invasive activity. Interestingly, the presence of 'normal' (not tumor-derived) stromal cells induced total tumor cell number reduction (P < 0.005) associated with a significant decrease in E-cadherin expression (P < 0.005). Conversely, beta-catenin expression was up-regulated (P < 0.01) in the presence of stromal cells with predominant cytoplasmic expression. Moreover, patient samples confirmed that these data recapitulated the clinical situation. In conclusion, pancreatic organotypic culture offers a reproducible, bio-mimetic, three-dimensional in vitro model that allows examination of the interactions between stromal elements and pancreatic cancer cells.
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