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Circulating tumor cells form metastases by reaching a distant microcirculation, undergoing transendothelial migration, entering into the remote tissue and proliferating. Microfluidic assays have recently been developed that enable the visualization and quantification of this process within vascular networks that recapitulate many aspects of the in vivo microcirculation. The assays are created by seeding endothelial cells in co-culture with fibroblasts or pericytes within a fibrin gel. In 1 day, the networks form, and in 4 to 7 days they are perfusable with medium. At that point, tumor cells, with or without accompanying immune cells, are streamed into the network, some fraction of which will arrest and extravasate into the surrounding matrix. Models of this type have been used to study several aspects of this process. These studies have provided detailed data on the ability of different tumor cell types to extravasate, the adhesion molecules they use to pull themselves through the endothelial monolayer, and the effects of various other cell types in the intravascular space (neutrophils and platelets), and the extracellular matrix (fibroblasts, pericytes, myoblasts, and osteoblasts). Some studies have been carried out for over one week in order to observe the initial stages of growth of the metastatic tumor. Other vascular network models have also been developed that can be used for longer-term studies, with more realistic network morphologies and remodeled matrix composition.
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