Pericellular proteases have long been associated with cancer invasion and metastasis due to their ability to degrade extracellular matrix components. Recent studies demonstrate that proteases also modulate tumor progression and metastasis through highly regulated and complex processes involving cleavage, processing, or shedding of cell adhesion molecules, growth factors, cytokines, and kinases. In this review, we address how cancer cells, together with their surrounding microenvironment, regulate pericellular proteolysis. We dissect the multitude of mechanisms by which pericellular proteases contribute to cancer progression and discuss how this knowledge can be integrated into therapeutic opportunities.
Keywords: invasion; macrophages; metastasis; migration; proteases; tumor microenvironment.
© 2014 Sevenich and Joyce; Published by Cold Spring Harbor Laboratory Press.