The study investigates the role of the perivascular niche in regulating breast tumor dormancy. Researchers found that dormant tumor cells (DTCs) reside on the microvasculature of lung, bone marrow, and brain in mice. They engineered organotypic microvascular niches to determine if endothelial cells directly influence breast cancer cell (BCC) growth. The results showed that endothelial-derived thrombospondin-1 (TSP-1) induces sustained BCC quiescence, while sprouting neovasculature accelerates BCC outgrowth. TSP-1 was diminished near sprouting neovasculature, suggesting a loss of tumor suppression. Time-lapse analysis confirmed that tumor growth was accelerated around neovascular tips, which are rich in tumor-promoting factors such as active TGF-β1 and periostin (POSTN). These findings suggest that stable microvasculature constitutes a 'dormant niche,' while sprouting neovasculature sparks micrometastatic outgrowth. The study also identified neovascular tips as 'micrometastatic niches' enriched for POSTN and active TGF-β1, which promote BCC growth. Maintaining vascular homeostasis is crucial for sustaining DTC dormancy.The study investigates the role of the perivascular niche in regulating breast tumor dormancy. Researchers found that dormant tumor cells (DTCs) reside on the microvasculature of lung, bone marrow, and brain in mice. They engineered organotypic microvascular niches to determine if endothelial cells directly influence breast cancer cell (BCC) growth. The results showed that endothelial-derived thrombospondin-1 (TSP-1) induces sustained BCC quiescence, while sprouting neovasculature accelerates BCC outgrowth. TSP-1 was diminished near sprouting neovasculature, suggesting a loss of tumor suppression. Time-lapse analysis confirmed that tumor growth was accelerated around neovascular tips, which are rich in tumor-promoting factors such as active TGF-β1 and periostin (POSTN). These findings suggest that stable microvasculature constitutes a 'dormant niche,' while sprouting neovasculature sparks micrometastatic outgrowth. The study also identified neovascular tips as 'micrometastatic niches' enriched for POSTN and active TGF-β1, which promote BCC growth. Maintaining vascular homeostasis is crucial for sustaining DTC dormancy.