161697 20260126150158.0 doi 10.1038/s41598-025-03504-8 sideral 144375 ART-2025-144375 eng Guerrero-López, Paula Universidad de Zaragoza (orcid)0000-0003-3661-7718 2D versus 3D tumor-on-chip models to study the impact of tumor organization on metabolic patterns in vitro 2025 Access copy available to the general public Unrestricted Despite the limitations of in vitro models to investigate cancer cell metabolism, their study can provide new insights essential for understanding tumorigenesis and effectively aiding in the development of novel therapies. The innovative tumor-on-chip models offer a more physiologically relevant platform than the traditional 2D cultures. These 3D cultures incorporate cell–cell and cell–matrix interactions, as well as diffusion dynamics through both the matrix and tumor spheroid, modeling in vivo diffusion within the tumor. Therefore, this work focuses on a quantitative comparison between 2D and 3D cultures through a microfluidic chip that allows daily monitoring of cancer cell key metabolites such as glucose, glutamine and lactate, unveiling critical differences. Our analysis reveals reduced proliferation rates in 3D models, likely due to limited diffusion of nutrients and oxygen. Additionally, 3D cultures showed distinct metabolic profiles, including elevated glutamine consumption under glucose restriction and higher lactate production, indicating an enhanced Warburg effect. The microfluidic chip enabled continuous monitoring, revealing increased per-cell glucose consumption in 3D models, highlighting fewer but more metabolically active cells than in 2D cultures. These findings underscore the importance of using microfluidic-based 3D models to provide a more accurate representation of tumor metabolism and progression compared to traditional 2D cultures. info:eu-repo/grantAgreement/ES/MICINN-AEI-FEDER/PID2021-122409OB-C21 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Martín-Pardillos, Ana Universidad de Zaragoza Bonet-Aleta, Javier (orcid)0000-0002-1791-0188 Mosseri, Andrea Hueso, Jose L. Universidad de Zaragoza (orcid)0000-0002-4546-4111 Santamaria, Jesus Universidad de Zaragoza (orcid)0000-0002-8701-9745 Garcia-Aznar, Jose Manuel Universidad de Zaragoza (orcid)0000-0002-9864-7683 5005 555 Universidad de Zaragoza Dpto. Ing.Quím.Tecnol.Med.Amb. Área Ingeniería Química 5004 605 Universidad de Zaragoza Dpto. Ingeniería Mecánica Área Mec.Med.Cont. y Teor.Est. 5005 790 Universidad de Zaragoza Dpto. Ing.Quím.Tecnol.Med.Amb. Área Tecnologi. Medio Ambiente 1002 807 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Toxicología 15, 1 (2025), 18 pp. Sci. rep. (Nat. Publ. Group) Scientific reports (Nature Publishing Group) 2045-2322 9386153 http://zaguan.unizar.es/record/161697/files/texto_completo.pdf Versión publicada 1990748 http://zaguan.unizar.es/record/161697/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:161697 articulos driver 2026-01-26-14:59:59 ARTICLE