Publicaciones científicas

Tumor Organoids Grown in Mixed-Composition Hydrogels Recapitulate the Plasticity of Pancreatic Cancers

21-jul-2025 | Revista: Gels

Ioritz Sorzabal-Bellido 1, Xabier Morales 2, Iván Cortés-Domínguez 1 2 3 4, Maider Esparza 2, Lucía Grande 2, Pedro Castillo 1, Silvia Larumbe 5, María Monteserín 5, Shruthi Narayanan 6, Mariano Ponz-Sarvise 4 6 7, Silve Vicent 4 6 8 9, Carlos Ortiz-de-Solórzano 1 2 8 10


Abstract

Pancreatic ductal adenocarcinoma (PDAC) tumors exhibit pronounced phenotypic plasticity, alternating between a treatment-sensitive classical phenotype and a more aggressive basal-like state associated with drug resistance and poor prognosis. The frequent coexistence of these phenotypes complicates patient stratification and the selection of effective therapies. Tumor-derived organoids are valuable tools for drug screening; however, their clinical relevance relies on how accurately they recapitulate the phenotypic and functional characteristics of the original tumors. In this study, we present a quantitative analysis of how hydrogel composition influences the phenotype, tissue remodeling, metabolism, and drug resistance of PDAC organoids. Organoids were cultured within three types of hydrogels: Matrigel, collagen-I, and a mixture of collagen-I and Matrigel. Our results demonstrate that: (i) PDAC organoids grown in Matrigel exhibit a classical phenotype, with metabolic and drug response profiles similar to those of low-physiological two-dimensional cultures; (ii) Organoids grown in collagen-containing hydrogels, particularly those in collagen-Matrigel composites, faithfully recapitulate basal-like tumors, characterized by epithelial-to-mesenchymal transition, tissue remodeling, metabolic activity, and drug resistance; (iii) TGFβ induces an exacerbated, highly invasive basal-like phenotype. Summarizing, our findings highlight the importance of 3D hydrogel composition in modulating PDAC organoid phenotype and behavior and suggest collagen-Matrigel hydrogels as the most suitable matrix for modeling PDAC biology.

CITA DEL ARTÍCULO Gels. 2025 Jul 21;11(7):562. doi: 10.3390/gels11070562.

Nuestros autores

Dr. Xabier Morales Urteaga
Técnico de laboratorio Plataforma de Imagen
Dr. Iván Cortés Domínguez
Maider Esparza Borda
Técnico de laboratorio Plataforma de Imagen
Lucía Grande López
Técnico de laboratorio Plataforma de Imagen