Organ-Specific Colonization and Niche Remodeling in a Human Tissue Model of Metastasis

We established a human multi-tissue model of cancer spread, with engineered bone and lung linked to vascular flow and exposed to circulating cancer cells. Parental MDA-MB-231 cells extravasated towards both tissues, remodeled the 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.