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3D Bioprinted Tumor-Stroma Models of Triple-Negative Breast Cancer Stem Cells for Preclinical Targeted Therapy Evaluation

Authors: Patricia González-Callejo; Clara García-Astrain; Ada Herrero-Ruiz; Malou Henriksen-Lacey; Joaquín Seras-Franzoso; Ibane Abasolo; Luis M. Liz-Marzán;

3D Bioprinted Tumor-Stroma Models of Triple-Negative Breast Cancer Stem Cells for Preclinical Targeted Therapy Evaluation

Abstract

Breast cancer stem cells (CSCs) play a pivotal role in therapy resistance and tumor relapse, emphasizing the need for reliable in vitro models that recapitulate the complexity of the CSC tumor microenvironment to accelerate drug discovery. We present a bioprinted breast CSC tumor-stroma model incorporating triple-negative breast CSCs (TNB-CSCs) and stromal cells (human breast fibroblasts), within a breast-derived decellularized extracellular matrix bioink. Comparison of molecular signatures in this model with different clinical subtypes of bioprinted tumor-stroma models unveils a unique molecular profile for artificial CSC tumor models. We additionally demonstrate that the model can recapitulate the invasive potential of TNB-CSC. Surface-enhanced Raman scattering imaging allowed us to monitor the invasive potential of tumor cells in deep z-axis planes, thereby overcoming the depth-imaging limitations of confocal fluorescence microscopy. As a proof-of-concept application, we conducted high-throughput drug testing analysis to assess the efficacy of CSC-targeted therapy in combination with conventional chemotherapeutic compounds. The results highlight the usefulness of tumor-stroma models as a promising drug-screening platform, providing insights into therapeutic efficacy against CSC populations resistant to conventional therapies.

Keywords

Medicaments antineoplàstics - Ús terapèutic, Triple Negative Breast Neoplasms, Antineoplastic Agents, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos, Triple-negative breast cancer, Cell Line, Tumor, DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms, Tumor Microenvironment, Humans, FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::microambiente celular::microambiente tumoral, 3D bioprinting, Cancer stem cells, SERS, TECHNOLOGY, INDUSTRY, AND AGRICULTURE::Technology, Industry, and Agriculture::Technology::Printing, Three-Dimensional, Bioprinting, Tumor microenvironment, COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos, ANATOMÍA::células::células madre::células madre neoplásicas, Mama - Càncer - Tractament, PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment, Printing, Three-Dimensional, Neoplastic Stem Cells, TECNOLOGÍA, INDUSTRIA Y AGRICULTURA::tecnología, industria y agricultura::tecnología::impresión tridimensional, Female, Stromal Cells, Cèl·lules mare, Impressió 3D, ANATOMY::Cells::Stem Cells::Neoplastic Stem Cells, CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents

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    popularity
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    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
14
Top 10%
Average
Top 10%
Green
hybrid
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Cancer Research