Extracellular matrix determinants of proteolytic and non-proteolytic cell migration.
Cell invasion into the 3D extracellular matrix (ECM) is a multistep biophysical process involved in inflammation, tissue repair, and metastatic cancer invasion. Migrating cells navigate through tissue structures of complex and often varying physicochemical properties, including molecular composition, porosity, alignment and stiffness, by adopting strategies that involve deformation of the cell and engagement of matrix-degrading proteases. We review how the ECM determines whether or not pericellular proteolysis is required for cell migration, ranging from protease-driven invasion and secondary tissue destruction, to non-proteolytic, non-destructive movement that solely depends on cell deformability and available tissue space. These concepts call for therapeutic targeting of proteases to prevent invasion-associated tissue destruction rather than the migration process per se.
Department of Cell Biology, Nijmegen Center for Molecular Life Science, Radboud University Nijmegen, 6500 HB Nijmegen, The Netherlands. k.wolf@ncmls.ru.nl
Katarina
K
Wolf
Peter
P
Friedl
D000818:Animals; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010447:Peptide Hydrolases / Q000378:metabolism; D059748:Proteolysis
D016326:Extracellular Matrix Proteins; D010447:Peptide Hydrolases