Table 1.
Engineering design considerations and models used for various steps in tumor initiation, progression, and metastasis
| Biological event | Engineering considerations | Models used |
|---|---|---|
| Tumor initiation and growth | • ECM composition and stiffness | • 3D spheroid assay |
| • Compressive stress | • Hanging drop assay | |
| • Adhesion molecule density | ||
| Blood and lymphangiogenesis | • Endothelial sprouting into 3D ECM | • Bead assay |
| • Growth factor gradients | • Tubulogenesis assays | |
| • Luminal and interstitial flow | • Microfluidic devices | |
| • Role of macrophages, stromal fibroblasts, and other cells | • 3D flow chambers | |
| Cell invasion and chemotaxis | • Cell contraction and motility | • Modified Boyden chamber |
| • Interstitial flow and ECM stress | • 3D cell tracking | |
| • Co-culture with stromal cells | • Microfluidic devices | |
| • 3D matrix, stiffness, adhesion molecule density | • Vertical layered assay | |
| • Oxygen gradients/hypoxia | ||
| • Chemokine gradients | ||
| Intravasation into blood or lymphatic vessels | • Interactions between tumor cells and endothelial cells | • Modified Boyden chamber |
| • ECM composition; presence of basement membrane | • Microfluidic devices | |
| • Transendothelial flow (e.g., into lymphatic vessels) | ||
| • Luminal flow on endothelial cells | ||
| Tumor cell circulation | • Luminal shear stresses | • Microfluidic flow chamber |
| • Complex geometry (e.g., branching, narrowing capillaries) | ||
| • Platelets, blood cells, clotting factors | ||
| Adhesion and extravasation | • Co-culture with endothelial cells | • Parallel plate flow chamber |
| • Luminal flow | ||
| • Chemokines and adhesion molecules | ||
| Growth in ectopic site | • Tissue-specific features of ectopic site (e.g., lymph node, liver, brain, bone) including chemokines and ECM components | • 3D cultures |