01967nas a2200301   4500000000100000008004100001260001500042100002100057700002300078700001700101700002600118700002000144700001600164700001700180700002200197700002300219700001900242700001600261700002100277700002000298700001800318700002900336245009100365856006100456300001300517490000700530520112800537       2026                            d  c2026-08-191 aAlan G. Chramiec1 aIlaria Baldassarri1 aEce Öztürk1 aDaniel Naveed Tavakol1 aMiranda C. Wang1 aMax Summers1 aKeith Yeager1 aRichard Z. Zhuang1 aAnushka Srivastava1 aSomnath Tagore1 aDiogo Teles1 aHanina Hibshoosh1 aAndrea Califano1 aPeter A. Sims1 aGordana Vunjak-Novakovic00aOrgan-specific colonization and niche remodeling in a human tissue model of metastasis  uhttps://www.science.org/doi/10.1126/scitranslmed.adv6871  aeadv68710 v183 aFor metastatic colonization to occur, disseminated tumor cells must survive, adapt to, and remodel distant microenvironments in an organ-specific manner. We established a human multitissue model of cancer spread, with engineered bone and lung linked by vascular flow containing circulating cancer cells. Parental MDA-MB-231 cells extravasated toward both tissues, remodeled their niches, and acquired transcriptional programs reflecting adaptation to the local microenvironment, particularly upon homing to bone. Tissue-specific colonization by the bone- and lung-tropic MDA-MB-231 derivatives was quantified in independently perfused bone or lung platforms. Consistent with in vivo behavior, bone-tropic cells showed stronger bone colonization than lung-tropic cells and induced more pronounced osteolysis. In contrast, lung-tropic cells caused greater epithelial disruption in lung tissue and only modest colonization of bone. Distinct patterns of tissue colonization and secreted factors demonstrate that this device recapitulates key features of organ-specific metastasis observed in vivo for this family of cell lines.