ArticleJournal of experimental & clinical cancer research : CR2019
Multiplex quantitative analysis of stroma-mediated cancer cell invasion, matrix remodeling, and drug response in a 3D co-culture model of pancreatic tumor spheroids and stellate cells.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 113 citations in OpenAlex.
- Harnessing human tumor organoids for cancer modeling and precision therapy.Protein & cell · 2026Review
- Review
- Research progress of plant-derived chemical compounds for overcoming pancreatic cancer drug resistance.World journal of gastroenterology · 2026Review
- A new inject-embed 3D culture method enables the spheroid and aggregate formation from single or dual liver cancer cell types.Cancer cell international · 2026Article
- O-GlcNAcylation of UGDH regulates its activity and remodels the extracellular matrix to facilitate tumor growth.Cell death and differentiation · 2026Article
- Functionalized Biomaterials in the Investigation of the Effects of Fluid Shear Forces in the Immune Regulation of Cancer Progression and Metastasis.Journal of functional biomaterials · 2026Review
- HCS-3DX, a next-generation AI-driven automated 3D-oid high-content screening system.Nature communications · 2025Article
- Patient-derived organoids in hepatobiliary pancreatic cancer research: Their uses and limitations.World journal of gastroenterology · 2025Article
- Biomimetic Tumour Model Systems for Pancreatic Ductal Adenocarcinoma in Relation to Photodynamic Therapy.International journal of molecular sciences · 2025Review
- Three-Dimensional Culture Systems in Neuroblastoma Research.Organoids · 2025Article
- Quantitative characterization of the 3D self-organization of PDAC tumor spheroids reveals cell type and matrix dependence through advanced microscopy analysis.APL bioengineering · 2025Article
- Patient-derived xenografts from circulating cancer stem cells as a preclinical model for personalized pancreatic cancer research.Scientific reports · 2025Article
- Construction and application of pancreatic exocrine organoid and spheroid for drug screening and precision medicine.Frontiers in cell and developmental biology · 2025Review
- Plasma-Activated Medium Inhibited the Proliferation and Migration of Non-Small Cell Lung Cancer A549 Cells in 3D Culture.International journal of molecular sciences · 2024Article
- Tumor-ColonizingBiomolecules · 2024Article
- Comparison Length of Linker in Compound for Nuclear Medicine Targeting Fibroblast Activation Protein as Molecular Target.International journal of molecular sciences · 2024Article
- Targeted Cancer Therapy-on-A-Chip.Advanced healthcare materials · 2024Review
- Tumor-microenvironment-on-a-chip: the construction and application.Cell communication and signaling : CCS · 2024Review
- Controlling cellular packing and hypoxia in 3D tumor spheroidsBiomaterials science · 2024Article
- DKK1-SE recruits AP1 to activate the target gene DKK1 thereby promoting pancreatic cancer progression.Cell death & disease · 2024Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) is a stroma-rich carcinoma, and pancreatic stellate cells (PSCs) are a major component of this dense stroma. PSCs play significant roles in metastatic progression and chemoresistance through cross-talk with cancer cells. Preclinical in vitro tumor model of invasive phenotype should incorporate three-dimensional (3D) culture of cancer cells and PSCs in extracellular matrix (ECM) for clinical relevance and predictability.
methodsPANC-1 cells were cultured as tumor spheroids (TSs) using our previously developed minipillar chips, and co-cultured with PSCs, both embedded in collagen gels. Effects of PSC co-culture on ECM fiber network, invasive migration of cancer cells, and expression of epithelial-mesenchymal transition (EMT)-related proteins were examined. Conditioned media was also analyzed for secreted factors involved in cancer cell-PSC interactions. Inhibitory effect on cancer cell invasion was compared between gemcitabine and paclitaxel at an equitoxic concentration in PANC-1 TSs co-cultured with PSCs.
resultsCo-culture condition was optimized for the growth of TSs, activation of PSCs, and their interaction. Increase in cancer cell invasion via ECM remodeling, invadopodia formation and EMT, as well as drug resistance was recapitulated in the TS-PSC co-culture, and appeared to be mediated by cancer cell-PSC interaction via multiple secreted factors, including IL-6, IL-8, IGF-1, EGF, TIMP-1, uPA, PAI-1, and TSP-1. Compared to gemcitabine, paclitaxel showed a greater anti-invasive activity, which was attributed to suppresion of invadopodia formation in cancer cells as well as to PSC-specific cytotoxicity abrogating its paracrine signaling.
conclusionsHere, we established 3D co-culture of TSs of PANC-1 cells and PSCs using minipillar histochips as a novel tumoroid model of PDAC. Our results indicate usefulness of the present co-culture model and multiplex quantitative analysis method not only in studying the role of PSCs and their interactions with tumor cell towards metastatic progression, but also in the drug evaluation of stroma-targeting drugs.
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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.