Chapter 10: Microfluidic Models of the Tumor Microenvironment

Advancing our understanding of the metastasis-promoting properties of the tumor microenvironment (TME) requires mechanistic studies of tumor biology and functional responses at the cellular, sub-cellular, and molecular levels. Microfluidic models offer several advantages over traditional in vitro and in vivo platforms including the incorporation of fluid pressure and biomolecular concentration gradients, optical compatibility, and the specification of cellular and matrix compositions for more relevant 3D physiological recapitulation. For instance, microfluidics enables the application of highly controllable physicochemical properties such as gradients of oxygen (O₂) tension and oncogenic signaling molecules, fluid mechanical stimuli, and biophysical tissue matrix stiffness and solid stress. Microphysiological systems can be used to uncover the role of these tractable factors and the potent migratory cues they impart onto malignant cells, which promote and maintain cancer invasion. Consequently, there is significant interest in leveraging microfluidic models to develop novel therapies that target the TME as it relates to invasive and metastatic progression. Here, we examine the application of microfluidic systems, which have emerged as versatile in vitro disease models of the TME that enable unprecedented control of microenvironmental factors for systematic experimentation and predictive drug testing.