Engineering confining microenvironment for studying cancer metastasis

The physical microenvironment of cells plays a fundamental role in regulating cellular behavior and cell fate, especially in the context of cancer metastasis. For example, capillary deformation can destroy arrested circulating tumor cells while the dense extracellular matrix can form a physical barrier for invading cancer cells. Understanding how metastatic cancer cells overcome the challenges brought forth by physical confinement can help in developing better therapeutics that can put a stop to this migratory stage of the metastatic cascade. Numerous in vivo and in vitro assays have been developed to recapitulate the metastatic processes and study cancer cell migration in a confining microenvironment. In this review, we summarize some of the representative techniques and the exciting new findings. We critically review the advantages, as well as challenges associated with these tools and methodologies, and provide a guide on the applications that they are most suited for. We hope future efforts that push forward our current understanding on metastasis under confinement can lead to novel and more effective diagnostic and therapeutic strategies against this dreaded disease.