ArticlePloS one2016
Co-Culture of Tumor Spheroids and Fibroblasts in a Collagen Matrix-Incorporated Microfluidic Chip Mimics Reciprocal Activation in Solid Tumor Microenvironment.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 1 of them a synthesis that pooled it.
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Who cites it
147 citing papers in PubMed, 1 synthesis or guideline pooled it, 272 citations in OpenAlex.
- Tumor-on-chip and cancer microphysiological platforms: knowledge structure, thematic evolution, and the emergence of organoid-integrated models, 2010-2025.Frontiers in pharmacology · 2026Pooled it
- Glucose and Oxygen Availability Shape Growth and Architecture of Tumor Spheroids in a Microfluidic 3D Model.Annals of biomedical engineering · 2026Article
- Tumor-on-chip as a personalized platform for rapid drug testing in breast cancer.Cell reports. Medicine · 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
- Genipin-Crosslinked, Silane-Anchored 3D Tumor-Stroma Microtissues for High-Content On-Chip Drug Testing.Advanced healthcare materials · 2026Article
- Integration of Fibroblast-Populated Collagen Lattices and Perfusable Micro-Physiological Systems: A Mechanobiologically Unified Framework for Living Devices.Micromachines · 2026Review
- Modeling CAF-tumor interactions to overcome therapy resistance.Journal of experimental & clinical cancer research : CR · 2026Review
- From Spheroids to Tumor-on-a-Chip for Cancer Modeling and Therapeutic Testing.Micromachines · 2025Review
- Biomimetic Salivary Gland Cancer Spheroid Platform for In Vitro Recapitulation of Three-Dimensional Tumor-Stromal Interactions.Biomolecules · 2025Article
- Colorectal Cancer at the Crossroads: The Good, the Bad, and the Future of Platinum-Based Drugs.Chemical reviews · 2025Review
- Cancer‑associated fibroblasts in human malignancies, with a particular emphasis on sarcomas (Review).International journal of oncology · 2025Review
- Cancer-on-a-chip for precision cancer medicine.Lab on a chip · 2025Review
- Review
- The Role of Organoids in Advancing Colorectal Cancer Research: Insights and Future Directions.Cancers · 2025Review
- 2D versus 3D tumor-on-chip models to study the impact of tumor organization on metabolic patterns in vitro.Scientific reports · 2025Article
- Classification of differentially activated groups of fibroblasts using morphodynamic and motile features.APL bioengineering · 2025Article
- Bone-on-a-Chip Systems for Hematological Cancers.Biosensors · 2025Review
- Advances in nanotechnology for targeting cancer-associated fibroblasts: A review of multi-strategy drug delivery and preclinical insights.APL bioengineering · 2025Review
- Quantitative characterization of the 3D self-organization of PDAC tumor spheroids reveals cell type and matrix dependence through advanced microscopy analysis.APL bioengineering · 2025Article
- Article
87 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multicellular 3D culture and interaction with stromal components are considered essential elements in establishing a 'more clinically relevant' tumor model. Matrix-embedded 3D cultures using a microfluidic chip platform can recapitulate the microscale interaction within tumor microenvironments. As a major component of tumor microenvironment, cancer-associated fibroblasts (CAFs) play a role in cancer progression and drug resistance. Here, we present a microfluidic chip-based tumor tissue culture model that integrates 3D tumor spheroids (TSs) with CAF in proximity within a hydrogel scaffold. HT-29 human colorectal carcinoma cells grew into 3D TSs and the growth was stimulated when co-cultured with fibroblasts as shown by 1.5-folds increase of % changes in diameter over 5 days. TS cultured for 6 days showed a reduced expression of Ki-67 along with increased expression of fibronectin when co-cultured with fibroblasts compared to mono-cultured TSs. Fibroblasts were activated under co-culture conditions, as demonstrated by increases in α-SMA expression and migratory activity. When exposed to paclitaxel, a survival advantage was observed in TSs co-cultured with activated fibroblasts. Overall, we demonstrated the reciprocal interaction between TSs and fibroblasts in our 7-channel microfluidic chip. The co-culture of 3D TS-CAF in a collagen matrix-incorporated microfluidic chip may be useful to study the tumor microenvironment and for evaluation of drug screening and evaluation.
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