Tumor vessels exhibit a wide range of structural and functional defects, which can influence the mechanism by which tumor cells enter the circulation. Due to the challenges associated with observing the dynamics of tumor-vessel interactions deep within tumors in real-time, Silvestri and colleagues developed a 3D tissue-engineered model where primary mammary tumor organoids are cocultured with a functional microvessel. Using fluorescence imaging, it was found that tumor organoids most frequently integrate within the endothelium through gaps in the basement membrane exposing tumor cells to microvessel flow. Other types of interactions observed were vessel constriction and vessel displacement. For details, see article by Silvestri and colleagues on page 4288.