ArticleBioengineering & translational medicine2022
TIMP-1-expressing breast tumor spheroids for the evaluation of drug penetration and efficacy.
Article in Bioengineering & translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 12 citations in OpenAlex.
- From barrier to guide: Exploiting disease-specific hemodynamics for enhanced nanodrug targeting in cardiovascular diseases.Pharmaceutical science advances · 2026Review
- Research progress on precision targeted therapy strategies for breast cancer based on tumor microenvironment.iScience · 2026Review
- In vivo dynamic nuclear polarization magnetic resonance imaging reveals cardiac mitochondrial redox imbalance as an early indicator of heart failure.Redox biology · 2026Article
- The dysadherin/carbonic anhydrase 9 axis shapes an acidic tumor microenvironment to promote colorectal cancer progression.Signal transduction and targeted therapy · 2026Article
- Formulation Strategies for Immunomodulatory Natural Products in 3D Tumor Spheroids and Organoids: Current Challenges and Emerging Solutions.Pharmaceutics · 2025Review
- Utility of Multicellular Spheroids for Investigating Mechanisms of Chemoresistance in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- ODSEI Chip: An Open 3D Microfluidic Platform for Studying Tumor Spheroid-Endothelial Interactions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Fabrication and Characterization of Electrospun DegraPolMaterials (Basel, Switzerland) · 2025Article
- Enhancing drug penetration in solid tumors via nanomedicine: Evaluation models, strategies and perspectives.Bioactive materials · 2024Review
- Modelling the complex nature of the tumor microenvironment: 3D tumor spheroids as an evolving tool.Journal of biomedical science · 2024Review
- Article
- Replacement, Reduction, and Refinement of Animal Experiments in Anticancer Drug Development: The Contribution of 3D In Vitro Cancer Models in the Drug Efficacy Assessment.Biomedicines · 2023Review
- TIMP-1-expressing breast tumor spheroids for the evaluation of drug penetration and efficacy.Bioengineering & translational medicine · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abundance of stromal cells and extracellular matrix (ECM) is observed in breast cancer, acting as a barrier for drug penetration and presenting a key issue for developing efficient therapeutics. In this study, we aimed to develop a three-dimensional (3D) multicellular tumor model comprising cancer and stromal cells that could effectively mimic the drug resistance properties of breast cancer. Three different types of spheroid models were designed by co-culturing breast cancer cells (MDA-MB-231) with three different types of stromal cells: human adipose-derived stromal cells (hASCs), human bone marrow stromal cells, or human dermal fibroblasts. Compared with other models, in the hASC co-culture model, tissue inhibitor of metalloproteinases-1 (TIMP-1) was highly expressed and the activity of matrix metalloproteinases was decreased, resulting in a higher ECM deposition on the spheroid surfaces. This spheroid model showed less drug penetration and treatment efficacy than the other models. TIMP-1 silencing in hASCs reduced ECM protein expression and increased drug penetration and vulnerability. A quantitative structure-activity relationship study using multiple linear regression drew linear relationships between the chemical properties of drugs and experimentally determined permeability values. Drugs that did not match the drug-likeness rules exhibited lower permeability in the 3D tumor model. Taken together, our findings indicate that this 3D multicellular tumor model may be used as a reliable platform for efficiently screening therapeutics agents for solid tumors.
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