A synthetic strategy for mimicking the extracellular matrix provides new insight about tumor cell migration

Abstract

Understanding the role of the tumor microenvironment during cancer progression and metastasis is complicated by interactions between cells, the extracellular matrix (ECM), and a variety of biomolecules. Using a synthetic strategy, we investigated proteolytic modes of migration for HT-1080 fibrosarcoma cells in an environment that limited confounding extracellular influences. A large percentage of HT-1080s migrated through a Rho kinase (ROCK)-dependent rounded morphology with a leading edge protrusion that defined the direction of migration, and migration was only weakly dependent on the adhesive peptide RGDS. HT-1080s migrating in thiol-ene hydrogels are more rounded and exhibit much more invasive behavior than dermal fibroblasts. Our results indicate that HT-1080s have the capacity to migrate through a mechanism that is distinct from mesenchymal cells, with significant amoeboid character even when utilizing a proteolytic migration strategy. The migration mode observed here provides insight into the invasiveness of metastatic cells in vivo and demonstrates the potential of a synthetic strategy for investigating complex biological problems.