Designer Biomaterials to Model Cancer Cell Invasion In Vitro: Predictive Tools or Just Pretty Pictures?

Metastasis is the leading cause of mortality in cancer patients. Underlying this process is the invasion and colonization of cancer cells into healthy tissues. Engineered hydrogel models of tumor microenvironments present an opportunity to understand the microenvironmental determinants of cellular invasion. The biochemical and mechanical cues, presented in the form of adhesion sites, degradable cues, matrix stiffness, and architecture, have significant effects on the extent of cancer cell migration, and the mechanisms employed by these cells to move through their matrix. Coculture with stromal cells such as cancer associated fibroblasts, endothelial cells, and immune cells that are associated with poor prognosis demonstrate that these cells exacerbate cancer cell invasion. With these models, researchers aim not only to recapitulate known cancer cell behaviors in a dish, but also to uncover new insights into mechanisms underlying these phenomena, paving the way for novel treatment strategies. In this perspective, the design of engineered models that are used to study cancer cell invasion and metastasis in vitro is discussed. To this end, the authors seek to understand and put into perspective: do these models reveal relevant mechanisms of cancer cell migration, or are they simply pretty pictures with little biological translatability?