Measuring reciprocal regulation of mesenchymal stem cell and tumor cell motility in two and three dimensions in vitro

Cell motility is central to many aspects of cell, tissue, and organ function in both health and disease. Examples include the morphogenetic events of embryogenesis, the functioning of the immune system, wound healing, angiogenesis, and the metastatic spread of cancer. Consequently, numerous methods have been developed to study cell motility. One rapidly growing area of interest in the cell motility field involves the interactions between tumor cells, surrounding stromal cells, and mesenchymal stem cells (MesSCs), which can be recruited to tumor sites. Important motility-related questions include how MesSCs are able to home to tumor sites, and, once present at a tumor site, how they affect the metastatic potential of the tumor cells. This chapter discusses and compares some of the more popular published experimental approaches to study cell motility, with an emphasis on assays that are suitable for studies of MesSC-tumor cell interactions in vitro. Both two-dimensional and three-dimensional cell motility assays are described, along with the specific strengths and weaknesses of each assay for interrogating specific subcomponents of the motility process. We also describe a novel murine breast cancer-MesSC model system that is well suited for in vitro, as well as in vivo studies of the motility events associated with tumor cell-MesSC interactions.