Abstract

Microphysiological Models for Metastatic Cancer

Roger Kamm, Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, Massachusetts Institute of Technology (MIT)

Circulating tumor cells form metastases by reaching a distant microcirculation, undergoing transendothelial migration, entering the remote tissue and proliferating.  Microfluidic assays have been developed to visualize and quantify this process within vascular networks that recapitulate aspects of the in vivo microcirculation.  Tumor cells, with or without accompanying immune cells, are streamed into a vascular network grown in a 3D matrix, some fraction of which arrest and extravasate into the surrounding matrix. These studies provide detailed information on the ability of different tumor cell types to extravasate, the adhesion molecules they use, and the effects of various other cell types in the intravascular and extravascular spaces.  While these models are largely organ-independent, work has also begun to investigate the specificity of certain cancers to metastasize to organs such as the brain.  For this purpose, a model of the blood-brain barrier has been produced, characterized in terms of its morphology and vascular permeability, and then used it to explore extravasation and tumor formation with the brain as the target organ.