000153143 001__ 153143
000153143 005__ 20251017144651.0
000153143 0247_ $$2doi$$a10.1063/5.0242490
000153143 0248_ $$2sideral$$a143573
000153143 037__ $$aART-2025-143573
000153143 041__ $$aeng
000153143 100__ $$aHernández-Hatibi, Soraya
000153143 245__ $$aQuantitative characterization of the 3D self-organization of PDAC tumor spheroids reveals cell type and matrix dependence through advanced microscopy analysis
000153143 260__ $$c2025
000153143 5060_ $$aAccess copy available to the general public$$fUnrestricted
000153143 5203_ $$aPancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant tumor-associated stroma composed from pancreatic stellate cells, which play a critical role in tumor progression. Developing accurate in vitro models requires understanding the complex interactions between tumor cells and their microenvironment. In this study, we present a quantitative imaging-based characterization of the three dimensional (3D) self-organization of PDAC tumour spheroids using a microfluidic platform that mimics key aspects of the tumor microenvironment. Our model incorporates collagen type I hydrogels to recreate the extracellular matrix, activated human pancreatic stellate cells (HPSCs), and various tumor cell types. Advanced imaging techniques, including Lattice Lightsheet Microscopy, allowed us to analyze the 3D growth and spatial organization of the spheroids, revealing intricate biomechanical interactions. Our results indicate that alterations in matrix properties—such as stiffness, pore size, and hydraulic permeability—due to variations in collagen concentration significantly influence the growth patterns and organization of PDAC spheroids, depending on tumor subtype and epithelial–mesenchymal phenotype. Higher collagen concentrations promoted larger spheroids in epithelial-like cell lines, while mesenchymal-type cells required increased collagen for self-organization into smaller spheroids. Furthermore, coculture with HPSCs affected spheroid formation distinctly based on each PDAC cell line's genetic and phenotypic traits. HPSCs had opposing effects on epithelial-like cell lines: one cell line exhibited enhanced spheroid growth, while another showed inhibited formation, whereas mesenchymal-like spheroids showed minimal impact. These results provide insights into tumor–stroma interactions, emphasizing the importance of the cell-specific and matrix-dependent factors for advancing our understanding of PDAC progression and informing future therapeutic strategies.
000153143 536__ $$9info:eu-repo/grantAgreement/ES/AEI/FJC2021-048046-I$$9info:eu-repo/grantAgreement/EC/H2020/101018587/EU/Individual and Collective Migration of the Immune Cellular System/ICoMICS$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 101018587-ICoMICS$$9info:eu-repo/grantAgreement/ES/ISCIII/PI20-00625$$9info:eu-repo/grantAgreement/ES/ISCIII/PI23-00591$$9info:eu-repo/grantAgreement/ES/MICINN-AEI-FEDER/PID2021-122409OB-C21$$9info:eu-repo/grantAgreement/ES/MICINN/PRE2019-090264
000153143 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttps://creativecommons.org/licenses/by-nc/4.0/deed.es
000153143 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000153143 700__ $$0(orcid)0000-0002-3784-1140$$aBorau, Carlos$$uUniversidad de Zaragoza
000153143 700__ $$aMartínez-Bosch, Neus
000153143 700__ $$aNavarro, Pilar
000153143 700__ $$0(orcid)0000-0002-9864-7683$$aGarcía-Aznar, José Manuel$$uUniversidad de Zaragoza
000153143 700__ $$0(orcid)0000-0003-2612-9235$$aGuerrero, Pedro Enrique
000153143 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000153143 773__ $$g9, 1 (2025), 016116 [20 pp.]$$tAPL Bioengineering$$x2473-2877
000153143 8564_ $$s11394503$$uhttps://zaguan.unizar.es/record/153143/files/texto_completo.pdf$$yVersión publicada
000153143 8564_ $$s2602581$$uhttps://zaguan.unizar.es/record/153143/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000153143 909CO $$ooai:zaguan.unizar.es:153143$$particulos$$pdriver
000153143 951__ $$a2025-10-17-14:36:38
000153143 980__ $$aARTICLE