000165056 001__ 165056
000165056 005__ 20251204150239.0
000165056 0247_ $$2doi$$a10.1186/s40170-025-00413-2
000165056 0248_ $$2sideral$$a146469
000165056 037__ $$aART-2025-146469
000165056 041__ $$aeng
000165056 100__ $$aGuerrero-López, Paula$$uUniversidad de Zaragoza
000165056 245__ $$aMatrix composition and glucose availability cooperatively determine cancer spheroid bioenergetics in 3D hydrogels
000165056 260__ $$c2025
000165056 5060_ $$aAccess copy available to the general public$$fUnrestricted
000165056 5203_ $$aThe interplay between extracellular matrix (ECM) biophysical properties and nutrient availability is crucial in cancer metabolism, but the specific influence of different ECM components remains unclear. This study investigates how collagen and fibrin 3D hydrogels, with varying stiffness, alongside different glucose concentrations, differentially regulate the metabolic phenotype of A549 lung and Panc1 pancreatic cancer spheroids. We observed that while glucose availability predominantly dictates metabolic profiles in collagen-based matrices, particularly influencing A549 cell behavior, metabolic adaptation in fibrin hydrogels was co-regulated by matrix properties and glucose levels. Notably, lung cancer cells shifted towards glycolysis under high glucose in collagen, whereas pancreatic cancer cells, inherently more glycolytic, exhibited metabolic rigidity, especially under low glucose, irrespective of collagen stiffness. Conversely, fibrin matrices generally induced a less noticeable, more quiescent metabolic state in both cancer cells, particularly under glucose deprivation. Specifically, higher collagen concentrations tended to support anaerobic metabolism, especially under glucose scarcity. The findings of this study reveal a hierarchical interplay where ECM composition tunes the sensitivity of cancer cells to nutrient availability, underscoring the necessity of integrating both matrix-specific mechanical cues and nutrient gradients in advanced 3D tumor models for identifying context-dependent metabolic vulnerabilities. This could have potential implications for designing future effective therapeutic strategies targeting the tumor microenvironment.
000165056 536__ $$9info:eu-repo/grantAgreement/ES/MINECO-AEI-FEDER/PID2021-122409OB-C21
000165056 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
000165056 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000165056 700__ $$aDrobac, Gorana
000165056 700__ $$aSilva, Eduardo A.
000165056 700__ $$aHagland, Hanne R.
000165056 700__ $$0(orcid)0000-0002-9864-7683$$aGarcía-Aznar, José Manuel$$uUniversidad de Zaragoza
000165056 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000165056 773__ $$g13, 1 (2025), [19 pp.]$$tCancer and Metabolism$$x2049-3002
000165056 8564_ $$s4562723$$uhttps://zaguan.unizar.es/record/165056/files/texto_completo.pdf$$yVersión publicada
000165056 8564_ $$s1842413$$uhttps://zaguan.unizar.es/record/165056/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000165056 909CO $$ooai:zaguan.unizar.es:165056$$particulos$$pdriver
000165056 951__ $$a2025-12-04-14:40:10
000165056 980__ $$aARTICLE