000165849 001__ 165849 000165849 005__ 20260115140311.0 000165849 0247_ $$2doi$$a10.1007/s13402-025-01110-4 000165849 0248_ $$2sideral$$a147420 000165849 037__ $$aART-2025-147420 000165849 041__ $$aeng 000165849 100__ $$aSharko, Vira 000165849 245__ $$aMicrophysiological systems for metastasis research: a stepwise approach 000165849 260__ $$c2025 000165849 5060_ $$aAccess copy available to the general public$$fUnrestricted 000165849 5203_ $$aMetastasis, the leading cause of cancer-related mortality, is a complex process involving tumor cell detachment from the primary site, survival and dissemination through the circulation, and colonization of distant organs. At each stage, tumor cells face adaptive pressures from successive biological and biomechanical challenges in the local microenvironment, which collectively shape their progression. Traditional in vitro models often fail to replicate these dynamics, while animal models are limited by species differences and restricted real-time monitoring. Microphysiological systems (MPS) have emerged as powerful tools to address these limitations, delivering physiologically relevant cues and precise experimental control to recapitulate step-specific metastatic contexts. This review outlines recent advances in MPS designs for modeling critical hallmarks of metastasis, beginning with matrix interactions, stromal cells, and mechanical forces from the tumor microenvironment that drive epithelial-mesenchymal transition and invasion. The discussion then transitions to MPS that reproduce vascular physiology during intravasation, circulation, and extravasation, and concludes with organ-specific environments for studying colonization and organotropic behavior in the final stages of metastasis. Additionally, common MPS configurations, categorized into horizontal and vertical compartmental arrangements, and strategies for integrating vascularization are explored. Together, these advances highlight the potential of MPS in elucidating metastatic mechanisms and advancing targeted therapies. 000165849 536__ $$9info:eu-repo/grantAgreement/ES/AEI/PID2021-126051OB-C41 000165849 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es 000165849 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000165849 700__ $$0(orcid)0000-0003-2410-5678$$aOchoa, Ignacio$$uUniversidad de Zaragoza 000165849 700__ $$0(orcid)0000-0001-8056-5236$$aSolanas, Estela$$uUniversidad de Zaragoza 000165849 7102_ $$11003$$2443$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Histología 000165849 7102_ $$11003$$2027$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Anatom.Embriol.Humana 000165849 773__ $$g48, 6 (2025), 1631-1658$$tCellular oncology (2011)$$x2211-3428 000165849 8564_ $$s4015488$$uhttps://zaguan.unizar.es/record/165849/files/texto_completo.pdf$$yVersión publicada 000165849 8564_ $$s2317016$$uhttps://zaguan.unizar.es/record/165849/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000165849 909CO $$ooai:zaguan.unizar.es:165849$$particulos$$pdriver 000165849 951__ $$a2026-01-15-12:36:37 000165849 980__ $$aARTICLE