3D Engineered Biomimetic Platform for Characterization of Collective Invasion, Tumor Emboli Formation, and Lymphatic Dissemination

Goal: Emerging evidence in diverse tumor types establishes a link between lymphatic dissemination and collective tumor cell invasion. To simulate the biomechanical features of the tumor-lymphatic microenvironment, we developed a 3D tumor-lymphatic architecture biomimetic (T-LAB) platform. Methods: Mathematical and computational fluid dynamics modeling were used to determine the fluid flow, oscillatory flow-induced shear stress, and system pressure in the 3D-printed macrofluidics platform. Results: Various human breast cancer cell lines and human dermal lymphatic endothelial cells (HDLEC) were seeded on a matrix in the T-LAB and imaged for up to 96h to assess cell morphology, viability, migration, and invasion. Co-culture of inflammatory breast cancer cells with HDLEC in the T-LAB, determined to simulate the fluidic properties of the tumor lymphatic microenvironment, demonstrated tumor cell clusters/emboli formation and collective invasion similar to the clinicopathological features observed in patients. Conclusions: The 3D T-LAB model developed here can be used to culture any type of tumor cell to study topographical features that impact tumor-lymphatic interface, collective invasion, and lymphatic dissemination.