ArticleJournal of experimental & clinical cancer research : CR2018
Microfluidic co-culture of pancreatic tumor spheroids with stellate cells as a novel 3D model for investigation of stroma-mediated cell motility and drug resistance.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 187 citations in OpenAlex.
- A pancreatic cancer organoid-macrophage co-culture using starPEG-heparin hydrogel deciphers tumor-immune cell interactions.NPJ precision oncology · 2026Article
- Three-dimensional spheroid models in breast cancer: tumor microenvironment complexity, cancer stem cell-driven resistance, and translational model integration.Journal of translational medicine · 2026Review
- S100A4 promotes collective invasion of pancreatic ductal adenocarcinoma and its blockade suppresses metastasis.Cell communication and signaling : CCS · 2026Article
- Immune-driven stromal inflammation in pancreatic cancer within a microfluidic platform.Biofabrication · 2026Article
- Aquaporin-3 and aquaporin-5 impact the development of pancreatic ductal adenocarcinoma spheroids.FEBS open bio · 2026Article
- Effective approaches in conquering chemoresistance of glioblastoma: potential for nanoformulations.Drug delivery and translational research · 2026Review
- Exploring the interplay between protein conformational changes and phosphorylation in a pancreatic cancer cell and stellate cell coculture system.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Effect of microbubble-assisted gemcitabine delivery with repeated ultrasound exposure in a pancreatic cancer organ-on-a-chip model.Scientific reports · 2025Article
- Review
- Bioengineering 3D Pancreatic Cancer Models with Fibrotic Stroma for In Vitro Cancer Modeling.Micromachines · 2025Review
- Pro-Apoptotic Effects of Unsymmetrical Bisacridines in 3D Pancreatic Multicellular Tumor Spheroids.International journal of molecular sciences · 2025Article
- Biomimetic Tumour Model Systems for Pancreatic Ductal Adenocarcinoma in Relation to Photodynamic Therapy.International journal of molecular sciences · 2025Review
- 2D versus 3D tumor-on-chip models to study the impact of tumor organization on metabolic patterns in vitro.Scientific reports · 2025Article
- Pancreatic 3D Organoids and Microfluidic Systems-Applicability and Utilization in Surgery: A Literature Review.Medicina (Kaunas, Lithuania) · 2025Review
- Mapping Tumor-Stroma-ECM Interactions in Spatially Advanced 3D Models of Pancreatic Cancer.ACS applied materials & interfaces · 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
- Conventional techniques and emerging nanotechnologies for early detection of cancer metastasis via epithelial-mesenchymal transition monitoring.National science review · 2025Review
- PI3Kα-specific inhibitor BYL-719 synergizes with cisplatin in vitro in PIK3CA-mutated ovarian cancer cells.Scientific reports · 2025Article
- A promising breakthrough in pancreatic cancer research: The potential of spheroids as 3D models.BioImpacts : BI · 2025Review
- Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPancreatic stellate cells (PSCs), a major component of the tumor microenvironment in pancreatic cancer, play roles in cancer progression as well as drug resistance. Culturing various cells in microfluidic (microchannel) devices has proven to be a useful in studying cellular interactions and drug sensitivity. Here we present a microchannel plate-based co-culture model that integrates tumor spheroids with PSCs in a three-dimensional (3D) collagen matrix to mimic the tumor microenvironment in vivo by recapitulating epithelial-mesenchymal transition and chemoresistance.
methodsA 7-channel microchannel plate was prepared using poly-dimethylsiloxane (PDMS) via soft lithography. PANC-1, a human pancreatic cancer cell line, and PSCs, each within a designated channel of the microchannel plate, were cultured embedded in type I collagen. Expression of EMT-related markers and factors was analyzed using immunofluorescent staining or Proteome analysis. Changes in viability following exposure to gemcitabine and paclitaxel were measured using Live/Dead assay.
resultsPANC-1 cells formed 3D tumor spheroids within 5 days and the number of spheroids increased when co-cultured with PSCs. Culture conditions were optimized for PANC-1 cells and PSCs, and their appropriate interaction was confirmed by reciprocal activation shown as increased cell motility. PSCs under co-culture showed an increased expression of α-SMA. Expression of EMT-related markers, such as vimentin and TGF-β, was higher in co-cultured PANC-1 spheroids compared to that in mono-cultured spheroids; as was the expression of many other EMT-related factors including TIMP1 and IL-8. Following gemcitabine exposure, no significant changes in survival were observed. When paclitaxel was combined with gemcitabine, a growth inhibitory advantage was prominent in tumor spheroids, which was accompanied by significant cytotoxicity in PSCs.
conclusionsWe demonstrated that cancer cells grown as tumor spheroids in a 3D collagen matrix and PSCs co-cultured in sub-millimeter proximity participate in mutual interactions that induce EMT and drug resistance in a microchannel plate. Microfluidic co-culture of pancreatic tumor spheroids with PSCs may serve as a useful model for studying EMT and drug resistance in a clinically relevant manner.
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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.