title: 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.
authors.affiliation: Department of Chemical and Biological Engineering, Howard Hughes Medical Institute, University of Colorado at Boulder, ECCH111, CB424, Boulder, CO 80309, USA. kristi.anseth@colorado.edu
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schwartz
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Fairbanks
authors.forename: Robert E
authors.initials: RE
authors.lastname: Rogers
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Rangarajan
authors.forename: Muhammad H
authors.initials: MH
authors.lastname: Zaman
authors.forename: Kristi S
authors.initials: KS
authors.lastname: Anseth
mesh_terms: D040761:Biomimetic Materials / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism*; D005354:Fibrosarcoma / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology* / Q000503:physiopathology*
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