ArticleBMC cancer2016
3D culture of Her2+ breast cancer cells promotes AKT to MAPK switching and a loss of therapeutic response.
Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Three-dimensional spheroid models in breast cancer: tumor microenvironment complexity, cancer stem cell-driven resistance, and translational model integration.Journal of translational medicine · 2026Review
- 3D Breast Cancer Spheroids Reveal Architecture-Dependent HER2 Expression and Signaling.Biology · 2025Article
- The microRNAs landscape of luminal B breast cancer cells in a three-dimensional microenvironment.Hereditas · 2025Article
- Dual-Dynamic Covalently Cross-Linked Polyglycerol Hydrogels for Tumor Spheroid Culture.Biomacromolecules · 2025Article
- Article
- Nanostructured Biomaterials in 3D Tumor Tissue Engineering Scaffolds: Regenerative Medicine and Immunotherapies.International journal of molecular sciences · 2024Review
- Three-DimensionalInternational journal of biological sciences · 2024Review
- Potential Biomarkers Associated with Prognosis and Trastuzumab Response in HER2+ Breast Cancer.Cancers · 2023Article
- Deciphering Common Traits of Breast and Ovarian Cancer Stem Cells and Possible Therapeutic Approaches.International journal of molecular sciences · 2023Review
- Low HER2 expression in normal breast epithelium enables dedifferentiation and malignant transformation via chromatin opening.Disease models & mechanisms · 2023Article
- Technical report: liquid overlay technique allows the generation of homogeneous osteosarcoma, glioblastoma, lung and prostate adenocarcinoma spheroids that can be used for drug cytotoxicity measurements.Frontiers in bioengineering and biotechnology · 2023Article
- Three-dimensional in vitro culture models in oncology research.Cell & bioscience · 2022Review
- Three-Dimensional 3D Culture Models in Gynecological and Breast Cancer Research.Frontiers in oncology · 2022Review
- Fatty acid synthase as a feasible biomarker for triple negative breast cancer stem cell subpopulation cultured on electrospun scaffolds.Materials today. Bio · 2021Article
- Patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer.Scientific reports · 2021Article
- Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy.Scientific reports · 2021Article
- Review
- Article
- Novel 2D and 3D Assays to Determine the Activity of Anti-Leishmanial Drugs.Microorganisms · 2020Article
- In Vitro Models for Studying Invasive Transitions of Ductal Carcinoma In Situ.Journal of mammary gland biology and neoplasia · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe Her2 receptor is overexpressed in up to 25 % of breast cancers and is associated with a poor prognosis. Around half of Her2+ breast cancers also express the estrogen receptor and treatment for such tumours can involve both endocrine and Her2-targeted therapies. However, despite preclinical data supporting the effectiveness of these agents, responses can vary widely in the clinical setting. In light of the increasing evidence pointing to the interplay between the tumour and its extracellular microenvironment as a significant determinant of therapeutic sensitivity and response here we investigated the impact of 3D matrix culture of breast cancer cells on their therapeutic sensitivity.
methodsA 3D Matrigel-based culture system was established and optimized for the growth of ER+/Her2+ breast cancer cell models. Growth of cells in response to trastuzumab and endocrine agents in 3D culture versus routine monolayer culture were assessed using cell counting and Ki67 staining. Endogenous and trastuzumab-modulated signalling pathway activity in 2D and 3D cultures were assessed using Western blotting.
resultsBreast cancer cells in 3D culture displayed an attenuated response to both endocrine agents and trastuzumab compared with cells cultured in traditional 2D monolayers. Underlying this phenomenon was an apparent matrix-induced shift from AKT to MAPK signalling; consequently, suppression of MAPK in 3D cultures restores therapeutic response.
conclusionThese data suggest that breast cancer cells in 3D culture display a reduced sensitivity to therapeutic agents which may be mediated by internal MAPK-mediated signalling. Targeting of adaptive pathways that maintain growth in 3D culture may represent an effective strategy to improve therapeutic response clinically.
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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.