ArticleCellular and molecular bioengineering2018
The Role of Desmoplasia and Stromal Fibroblasts on Anti-cancer Drug Resistance in a Microengineered Tumor Model.
Article in Cellular and molecular bioengineering, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 35 citations in OpenAlex.
- Multimodal profiling of CAR T cells against glioblastoma using a microengineered 3D tumor-on-a-chip model.Bioactive materials · 2026Article
- Rational Design of HER2-Targeted Combination Therapies to Reverse Drug Resistance in Fibroblast-Protected HER2+ Breast Cancer Cells.Cellular and molecular bioengineering · 2024Article
- Engineered Tumor-Immune Microenvironment On A Chip to Study T Cell-Macrophage Interaction in Breast Cancer Progression.Advanced healthcare materials · 2024Article
- Programming temporal stiffness cues within extracellular matrix hydrogels for modelling cancer niches.Materials today. Bio · 2024Article
- Engineered 3D ex vivo models to recapitulate the complex stromal and immune interactions within the tumor microenvironment.Biomaterials · 2024Review
- Improving the Efficacy of Common Cancer Treatments via Targeted Therapeutics towards the Tumour and Its Microenvironment.Pharmaceutics · 2024Review
- Cancer 3D Models for Metallodrug Preclinical Testing.International journal of molecular sciences · 2023Review
- Chemokine clouding and liver cancer heterogeneity: Does it impact clinical outcomes?Seminars in cancer biology · 2022Review
- Recent Developments in the Study of the Microenvironment of Cancer and Drug Delivery.Current drug metabolism · 2022Article
- NovelFrontiers in oncology · 2022Review
- Biomaterial-Assisted Regenerative Medicine.International journal of molecular sciences · 2021Review
- Microengineered 3D Tumor Models for Anti-Cancer Drug Discovery in Female-Related Cancers.Annals of biomedical engineering · 2021Review
- Proteinaceous Hydrogels for Bioengineering Advanced 3D Tumor Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Targeting Tumor-Stromal Interactions in Pancreatic Cancer: Impact of Collagens and Mechanical Traits.Frontiers in cell and developmental biology · 2021Review
- Fabrication Method of a High-Density Co-Culture Tumor-Stroma Platform to Study Cancer Progression.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Recapitulating pancreatic tumor microenvironment through synergistic use of patient organoids and organ-on-a-chip vasculature.Advanced functional materials · 2020Article
- Three-Dimensional Culture System of Cancer Cells Combined with Biomaterials for Drug Screening.Cancers · 2020Review
- Tumor microenvironment complexity and therapeutic implications at a glance.Cell communication and signaling : CCS · 2020Review
- Multiplex bioimaging of single-cell spatial profiles for precision cancer diagnostics and therapeutics.NPJ precision oncology · 2020Review
- A Human Organotypic Microfluidic Tumor Model Permits Investigation of the Interplay between Patient-Derived Fibroblasts and Breast Cancer Cells.Cancer research · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionCancer associated fibroblasts (CAFs) are known to participate in anti-cancer drug resistance by upregulating desmoplasia and pro-survival mechanisms within the tumor microenvironment. In this regard, anti-fibrotic drugs (i.e., tranilast) have been repurposed to diminish the elastic modulus of the stromal matrix and reduce tumor growth in presence of chemotherapeutics (i.e., doxorubicin). However, the quantitative assessment on impact of these stromal targeting drugs on matrix stiffness and tumor progression is still missing in the sole presence of CAFs.
methodsWe developed a high-density 3D microengineered tumor model comprised of MDA-MB-231 (highly invasive breast cancer cells) embedded microwells, surrounded by CAFs encapsulated within collagen I hydrogel. To study the influence of tranilast and doxorubicin on fibrosis, we probed the matrix using atomic force microscopy (AFM) and assessed matrix protein deposition. We further studied the combinatorial influence of the drugs on cancer cell proliferation and invasion.
resultsOur results demonstrated that the combinatorial action of tranilast and doxorubicin significantly diminished the stiffness of the stromal matrix compared to the control. The two drugs in synergy disrupted fibronectin assembly and reduced collagen fiber density. Furthermore, the combination of these drugs, condensed tumor growth and invasion.
conclusionIn this work, we utilized a 3D microengineered model to tease apart the role of tranilast and doxorubicin in the sole presence of CAFs on desmoplasia, tumor growth and invasion. Our study lay down a ground work on better understanding of the role of biomechanical properties of the matrix on anti-cancer drug efficacy in the presence of single class of stromal cells.
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