Combined experimental and mathematical approach for development of microfabrication-based cancer migration assay

Migration of cancer cells is a key determinant of metastasis, which is correlated with poor prognosis in patients. Evidence shows that cancer cell motility is regulated by stromal cell interactions. To quantify the role of homotypic and heterotypic cell-cell interaction in migration, a two-dimensional migration assay has been developed by microfabrication techniques. Two breast cancer cell lines, MDA-MB-231 and MDA-MB-453, were used to develop micropatterns of cancer cells (cell islands) that revealed distinct migration profiles in this assay. Although the individual migration rates of these cells showed only a sevenfold difference, MDA-MB-453 islands migrated significantly lower than MDA-MB-231 islands, indicating differential regulation of migration in isolated cells vs. islands. Island size had the greatest impact on migration, primarily for MDA-MB-231 cells. Migration of MDA-MB-231 islands was decreased by interaction with homotypic cells, and significantly more by heterotypic non-cancer-associated fibroblasts. In addition, a mathematical model of island migration in multi-cellular population has been developed using Stefan-Maxwell's equation. The model showed qualitative agreement with experimental results and predicted a biphasic relation between cell densities and island sizes. The combined experimental and mathematical model can be used to quantitatively study the impact of cell-cell interactions on migration.