FIG. 1.

Tissue engineering provides innovative tools to recreate tumor-inherent cell–microenvironment interactions in vitro. For example, hydrogel-based microfluidic three-dimensional (3D) culture systems provide spatiotemporal control over soluble factor presentation and allow studies of the role of chemical cues in tumor angiogenesis²³ (a: diffusion of rhodamine through a microfluidic collagen network [image courtesy of A.D. Stroock and N.W. Choi]). To probe the role of cell–cell interactions, micropatterning techniques allow culture of cells in the presence and absence of direct cell–cell contact³⁰ (b: Parylene peel-arrays patterned with fibronectin [green] and seeded with tumor cells [red]). Polymer-based artificial extracellular matrices can be used to broadly recreate 3D interactions of tumor cells with their surrounding extracellular matrix³ (c: tumor cells cultured within 3D porous poly [lactic-co-glycolic acid] scaffolds and stained with the viability stain calcein). To assess the role of tumor rigidity on tumor angiogenesis, traction force microscopy permits the quantification of cell-generated forces on matrices of varying elasticity⁸³ (d: traction force map of tumor-associated stroma cell [image courtesy of C.A. Reinhart-King and J.P. Califano]).