Controlled extracellular proteolysis of thrombospondins

Extracellular proteolysis in cancer: Proteases, substrates, and mechanisms in tumor progression and metastasis

“…While intact thrombospondin-1 exhibits anti-angiogenic and anti-metastatic properties, its proteolytic processing releases a variety of matrikines with divergent activities ( 313 ). Many proteases can release thrombospondin fragments containing an N-terminal heparin-binding domain ( 313 ), which are powerful stimulators of angiogenesis ( 314 , 315 ).…”

“…While intact thrombospondin-1 exhibits anti-angiogenic and anti-metastatic properties, its proteolytic processing releases a variety of matrikines with divergent activities ( 313 ). Many proteases can release thrombospondin fragments containing an N-terminal heparin-binding domain ( 313 ), which are powerful stimulators of angiogenesis ( 314 , 315 ). MT1-MMP production of thrombospondin-1 matrikines is crucial for intussusceptive angiogenesis, a microvasculature expansion observed in development, inflammatory diseases, and certain cancers ( 316 ).…”