Spontaneously formed in vitro MARY-X spheroids mimic the in vivo metastasis: (A; top and middle panels) In vitro, MARY-X forms a compact 3D multicellular structure in suspension, ranging in size from as small as 10 μm to as large as 400 μm in diameter (10× and 40× magnification, respectively). (A; bottom panel) FIB milling of the MARY-X spheroid displays extensive canalis structures throughout the MARY-X spheroid. Extensive surface microvilli (inset, arrow) adjacent to a canal as displayed in the FIB section (B; top and middle panels) A cross-section of a MARY-X primary tumor and murine lung metastases shows compact, multicellular MARY-X lymphovascular emboli (E) (H & E stained, 40× and 20× magnification). The pulmonary metastasis may exist as a simple single distinct lymphovascular embolus (middle panel; inset, E) or a more complex metastasis where the lymphovascular emboli are nestled within the murine surrounding stroma (middle panel, E). (B; bottom panel) Surface SEM of a cross-section of MARY-X emboli displays canalis with microvilli (inset).