3D Bioprinted Tumor-Stroma Models of Triple-Negative Breast Cancer Stem Cells for Preclinical Targeted Therapy Evaluation
González-Callejo, Patricia (Alianza Vasca de Investigación y Tecnología. CIC biomaGUNE)
García-Astrain, Clara (Alianza Vasca de Investigación y Tecnología. CIC biomaGUNE)
Herrero-Ruiz, Ada (Alianza Vasca de Investigación y Tecnología. CIC biomaGUNE)
Henriksen-Lacey, Malou (Alianza Vasca de Investigación y Tecnología. CIC biomaGUNE)
Seras-Franzoso, Joaquin (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Abasolo, Ibane (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Liz-Marzán, Luis M. (Hospital Universitari Vall d'Hebron. Institut de Recerca)

Date:	2024
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.
Grants:	European Commission 787510 European Commission 101138255 Agencia Estatal de Investigación FJCI-2016-28887 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-1173
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Triple-negative breast cancer ; Cancer stem cells ; 3D bioprinting ; Tumor microenvironment ; SERS
Published in:	ACS applied materials & interfaces, Vol. 16, Issue 21 (May 2024) , p. 27151-27163, ISSN 1944-8252

DOI: 10.1021/acsami.4c04135
PMID: 38764168

13 p, 3.4 MB

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