Metastasizing tumor cells must be able to squeeze through several narrow barriers, such as extracellular matrices and microvessels, on their way to secondary colony targets. During this process, the deformability of tumor cells is expected to play an important role. Microfluidics provides a unique opportunity to mimic in vivo cell squeezing and phenotype tumor cells based on their deformability. In this study, we developed a microfluidic device with arrays of microconstrictions. As cells flow through this multisqueezer device, we quantify cell sizes and phenotype them based on two deformability parameters – entry and transit time. We also determine the influence of channel wall friction on these two deformability parameters. We test the capabilities of the device with highly and weakly invasive prostate and breast cancer cells. We also assess the deformability of breast cancer cells that metastasize to the brain and those that do not.
We find that in general entry and transit times increase with cell size. Highly invasive prostate cancer cells CL1 have higher entry/transit times compared to lowly invasive LNCaP cells. A similar result is obtained for highly invasive breast cancer cells MB231 when tested against weakly invasive MCF7 cells. The multisqueezer device is also able to distinguish the breast cancer cells from pericardial effusion (HTB131) and brain metastasis (MB231BR). However, the device is unable to differentiate MB231BR (a subtype of MB231 cells that metastasize to brain only) and MB231 cells. These result suggest that the deformability metrics – entry and transit time – can distinguish at least some cancer cell lines. We hypothesize that differences in the frictional properties of MB231 and MB231BR might be more significant than differences in deformability allowing the MB231BR cells to cross the blood-brain barrier. We will test this hypothesis by coating the channel walls with polymers and results will be presented on the role of friction in tumor cell transport.