(228t) Investigating Cancer Cell Migration Guided By Stiffness Gradients

Metastasis is the primary cause of death in cancer patients; yet, there is a shortage of highly potent anti-metastatic drugs. Traditional cancer cell migration studies and screening for anti-metastatic compounds have been primarily performed using two-dimensional platforms that only allow cell migration along a single plane. However, spatial arrangement of in vivo biological signals are much more complicated, especially in scenarios where cell migration is guided by matrix stiffness gradients. In this work, we sought to develop a 2.5D culture platform where cells are placed at the interface between stiff TCPS and soft alginate to study the role of transitions in stiffness on cell migration. The 2.5D platform was used to study the effects of both matrix stiffness and cell-matrix adhesions on cell migration. We confirmed the roles of mechanotransductive signaling on cell migration using small molecule inhibitors of the RhoA-ROCK and Rac1 pathways, as well as the ability of cells to switch between adhesion dependent and independent modes using the integrin inhibitor, Cilengitide. The results reported in this study will facilitate the development of optimal in vitro platforms to discover therapeutic strategies against tumor cell motility and invasion.