Massachusetts Institute of Technology PS-OP
Understanding the fundamental mechanisms leading to metastatic cancer has been hampered by the need for models that replicate the in vivo situation, yet are amenable to tight control and facilitate high-resolution, time-lapse imaging and quantitative analysis of cell behavior. Over the past several years, we have developed microfluidic systems that are capable of simulating many steps of metastasis including tumor cell invasion, intravasation, trapping in the microcirculation or adhesion to the vessel walls, and extravasation into surrounding extracellular matrix. This prior work has shed new light on the interactions between a transmigrating tumor cell and the endothelium, the role of specific adhesion molecules, and the deformations of the cell and especially the cell nucleus, experience during the transmigration process. The object of our current study is to employ these assays in combination with new measurement methods to interrogate the changes in cell mechanics during the process of extravasation, and understand the nature of the cell-cell and cell-matrix force interactions. We are also investigating the nuclear deformations, changes in chromatin structure and the resulting changes in the transcriptome, which could have important implications for the subsequent ability of extravasated cells to form a new tumor.